ClinVar Genomic variation as it relates to human health
NM_001360016.2(G6PD):c.404A>C (p.Asn135Thr)
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_001360016.2(G6PD):c.404A>C (p.Asn135Thr)
Variation ID: 854215 Accession: VCV000854215.40
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 153763464 (GRCh37) [ NCBI UCSC ] X: 154535249 (GRCh38) [ 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 15, 2020 May 12, 2024 Nov 21, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001360016.2:c.404A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001346945.1:p.Asn135Thr missense NM_000402.4:c.494A>C NP_000393.4:p.Asn165Thr missense NM_001042351.3:c.404A>C NP_001035810.1:p.Asn135Thr missense NC_000023.11:g.154535249T>G NC_000023.10:g.153763464T>G NG_009015.2:g.17324A>C - Protein change
- N135T, N165T
- Other names
- G6PD Cairo
- p.Asn165Thr
- Canonical SPDI
- NC_000023.11:154535248:T:G
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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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
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
Help
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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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Aug 2, 2023 | RCV001059211.19 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 21, 2023 | RCV001091837.28 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 28, 2023 | RCV003467799.1 |
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
Help
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
Help
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
Help
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: SCV002599329.1
First in ClinVar: Nov 13, 2022 Last updated: Nov 13, 2022 |
Comment:
Variant found in unrelated hemizygotes with deficiency, anemia, and favism (PS4_M, PP4). Decreased activity in red blood cells (4-20%) (PS3). Predicted to be damaging by … (more)
Variant found in unrelated hemizygotes with deficiency, anemia, and favism (PS4_M, PP4). Decreased activity in red blood cells (4-20%) (PS3). Predicted to be damaging by SIFT and probably damaging by PolyPhen (PP3). Below expected carrier frequency in gnomAD (PM2). Reported as pathogenic by CeGaT (PP5). Post_P 0.997 (odds of pathogenicity 3155, Prior_P 0.1). (less)
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Pathogenic
(Apr 28, 2023)
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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: SCV004195405.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(May 02, 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: SCV003822585.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Aug 02, 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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Invitae
Accession: SCV001223828.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, … (more)
For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 854215). This variant is also known as G6PD Cairo. This missense change has been observed in individual(s) with glucose-6-phosphate dehydrogenase deficiency (PMID: 22906837, 27519946). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 135 of the G6PD protein (p.Asn135Thr). (less)
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Pathogenic
(Nov 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001472687.2
First in ClinVar: Jan 26, 2021 Last updated: Feb 20, 2024 |
Comment:
The G6PD c.404A>C; p.Asn135Thr variant (rs782322505), also known as c.494A>C; p.Asn165Thr (NM_000402.4) and G6PD Cairo, is reported in the literature in several children with acute … (more)
The G6PD c.404A>C; p.Asn135Thr variant (rs782322505), also known as c.494A>C; p.Asn165Thr (NM_000402.4) and G6PD Cairo, is reported in the literature in several children with acute hemolytic anemia induced by favism; all affected children demonstrated hyperbilirubinemia and were deficient for G6PD enzyme activity (Al-Sweedan 2012, Beutler 2002, Doss 2016, Reading 2016, Sirdah 2017). This variant is reported in ClinVar (Variation ID: 854215) and is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses predict that this variant is deleterious (REVEL: 0.887). Based on available information, this variant is considered to be pathogenic. References: Al-Sweedan SA et al. Molecular characterization of glucose-6-phosphate dehydrogenase deficiency among Jordanians. Acta Haematol. 2012 128:195-202. PMID: 22906837. Beutler E et al. Hematologically important mutations: glucose-6-phosphate dehydrogenase. Blood Cells Mol Dis. 2002 28:93-103. PMID: 12064901. Doss CG et al. Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World. Sci Rep. 2016 6:37284. PMID: 27853304. Reading NS et al. Favism, the commonest form of severe hemolytic anemia in Palestinian children, varies in severity with three different variants of G6PD deficiency within the same community. Blood Cells Mol Dis. 2016 60:58-64. PMID: 27519946. Sirdah MM et al. Possible association of 3' UTR +357 A>G, IVS11-nt 93 T>C, c.1311 C>T polymorphism with G6PD deficiency. Hematology. 2017 22:370-374. PMID: 28059001. (less)
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Pathogenic
(Jun 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248071.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Comment:
G6PD: PM2, PM5, PS3:Moderate, PS4:Moderate, PP1, PP4
Number of individuals with the variant: 3
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Pathogenic
(Jul 15, 2021)
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no assertion criteria provided
Method: clinical testing
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV004243585.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Number of individuals with the variant: 1
Age: 0-9 years
Sex: male
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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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Seven novel glucose-6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population. | Malik S | Human genomics | 2021 | PMID: 34620237 |
Favism, the commonest form of severe hemolytic anemia in Palestinian children, varies in severity with three different variants of G6PD deficiency within the same community. | Reading NS | Blood cells, molecules & diseases | 2016 | PMID: 27519946 |
Molecular characterization of glucose-6-phosphate dehydrogenase deficiency among Jordanians. | Al-Sweedan SA | Acta haematologica | 2012 | PMID: 22906837 |
Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Gaza Strip Palestinians. | Sirdah M | Blood cells, molecules & diseases | 2012 | PMID: 22770933 |
Text-mined citations for rs782322505 ...
HelpRecord last updated Jun 10, 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.