ClinVar Genomic variation as it relates to human health
NM_000402.4(G6PD):c.1250G>A (p.Arg417His)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000402.4(G6PD):c.1250G>A (p.Arg417His)
Variation ID: 10376 Accession: VCV000010376.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154532694 (GRCh38) [ NCBI UCSC ] X: 153760909 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Feb 14, 2024 Mar 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001360016.2:c.1160G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001346945.1:p.Arg387His missense NM_000402.4:c.1250G>A NP_000393.4:p.Arg417His missense NM_001042351.3:c.1160G>A NP_001035810.1:p.Arg387His missense NC_000023.11:g.154532694C>T NC_000023.10:g.153760909C>T NG_009015.2:g.19879G>A - Protein change
- R387H, R417H
- Other names
- G6PD, ARG387HIS
- G6PD Beverly Hills
- G6PD Genova
- G6PD Iwate
- G6PD Niigata
- G6PD Yamaguchi
- Canonical SPDI
- NC_000023.11:154532693:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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G6PD | - | - |
GRCh38 GRCh37 |
636 | 948 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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G6PD BEVERLY HILLS
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other (1) |
no assertion criteria provided
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Apr 18, 2013 | RCV000011100.1 |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2023 | RCV001857328.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 9, 2022 | RCV003466848.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Aug 12, 2022)
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criteria provided, single submitter
Method: curation
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: yes
Allele origin:
unknown
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Dunham Lab, University of Washington
Accession: SCV002599365.1
First in ClinVar: Nov 13, 2022 Last updated: Nov 13, 2022 |
Comment:
Variant found in unrelated hemizygotes with deficiency and CNSHA (PS4_M, PP4). Decreased activity in red blood cells (0-4%) (PS3). Within dimer interface (PM1). Predicted to … (more)
Variant found in unrelated hemizygotes with deficiency and CNSHA (PS4_M, PP4). Decreased activity in red blood cells (0-4%) (PS3). Within dimer interface (PM1). Predicted to be damaging or deleterious by multiple computational algorithms (PP3). Not found in gnomAD (PM2). Reported as pathogenic by Invitae (PP5). Post_P 0.999 (odds of pathogenicity 13661, Prior_P 0.1). (less)
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Pathogenic
(Jul 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Malaria, susceptibility to
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004195412.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV004236210.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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Pathogenic
(May 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002146487.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg387 amino acid residue in G6PD. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg387 amino acid residue in G6PD. Other variant(s) that disrupt this residue have been observed in individuals with G6PD-related conditions (PMID: 1611091), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt G6PD protein function. This variant has been observed in individual(s) with G6PD deficiency (PMID: 2602358, 12187030, 29248304, Invitae). ClinVar contains an entry for this variant (Variation ID: 10376). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with histidine at codon 387 of the G6PD protein (p.Arg387His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. (less)
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other
(Apr 18, 2013)
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no assertion criteria provided
Method: literature only
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G6PD BEVERLY HILLS
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000031327.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Hirono et al. (1989) demonstrated a G-to-A mutation at nucleotide 1160, causing substitution of histidine for arginine-387. The mutation destroyed an HhaI site.
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Prediction of functional consequences of the five newly discovered G6PD variations in Taiwan. | Chiu YH | Data in brief | 2019 | PMID: 31294066 |
Glucose-6-Phosphate Dehydrogenase Deficiency Mimicking Atypical Hemolytic Uremic Syndrome. | Walsh PR | American journal of kidney diseases : the official journal of the National Kidney Foundation | 2018 | PMID: 29248304 |
Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency. | Lee J | Annals of laboratory medicine | 2017 | PMID: 28028996 |
Chronic haemolytic anaemia and glucose-6 phosphate dehydrogenase deficiency. Case report and review of the literature. | Hundsdoerfer P | Acta haematologica | 2002 | PMID: 12187030 |
Several mutations including two novel mutations of the glucose-6-phosphate dehydrogenase gene in Polish G6PD deficient subjects with chronic nonspherocytic hemolytic anemia, acute hemolytic anemia, and favism. | Jablonska-Skwiecinska E | Human mutation | 1999 | PMID: 10571945 |
Clinical and haematological consequences of recurrent G6PD mutations and a single new mutation causing chronic nonspherocytic haemolytic anaemia. | Vulliamy TJ | British journal of haematology | 1998 | PMID: 9674740 |
Molecular analysis of eight biochemically unique glucose-6-phosphate dehydrogenase variants found in Japan. | Hirono A | Blood | 1997 | PMID: 9192788 |
New glucose-6-phosphate dehydrogenase mutations associated with chronic anemia. | Mason PJ | Blood | 1995 | PMID: 7858267 |
Molecular study of eight Japanese cases of glucose-6-phosphate dehydrogenase deficiency by nonradioisotopic single-strand conformation polymorphism analysis. | Hirono A | Blood | 1994 | PMID: 8193373 |
New glucose-6-phosphate dehydrogenase mutations from various ethnic groups. | Beutler E | Blood | 1992 | PMID: 1611091 |
A new glucose-6-phosphate dehydrogenase variant with congenital nonspherocytic hemolytic anemia (G6PD Genova). Biochemical characterization and mosaicism expression in the heterozygote. | Gaetani GF | Human genetics | 1990 | PMID: 2307454 |
Identification of the binding domain for NADP+ of human glucose-6-phosphate dehydrogenase by sequence analysis of mutants. | Hirono A | Proceedings of the National Academy of Sciences of the United States of America | 1989 | PMID: 2602358 |
A new glucose-6-phosphate dehydrogenase variant (G6PD Iwate) associated with congenital non-spherocytic hemolytic anemia. | Kanno H | Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society | 1988 | PMID: 3201886 |
Glucose 6-phosphate dehydrogenase variants in Japan. | Miwa S | Hemoglobin | 1980 | PMID: 7440223 |
Four new electrophoretically slow-moving glucose 6-phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: Gd(-) Kurume, Gd(-) Fukushima, Gd(-) Yamaguchi and Gd(-) Wakayama. | Miwa S | American journal of hematology | 1978 | PMID: 736032 |
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Text-mined citations for rs137852321 ...
HelpRecord last updated Mar 30, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.