ClinVar Genomic variation as it relates to human health
NM_001164277.2(SLC37A4):c.59G>A (p.Gly20Asp)
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_001164277.2(SLC37A4):c.59G>A (p.Gly20Asp)
Variation ID: 68286 Accession: VCV000068286.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q23.3 11: 119029311 (GRCh38) [ NCBI UCSC ] 11: 118900021 (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 Oct 22, 2013 Feb 14, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001164277.2:c.59G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001157749.1:p.Gly20Asp missense NM_001164278.2:c.59G>A NP_001157750.1:p.Gly20Asp missense NM_001164279.2:c.-172+81G>A intron variant NM_001164280.2:c.59G>A NP_001157752.1:p.Gly20Asp missense NM_001467.6:c.59G>A NP_001458.1:p.Gly20Asp missense NC_000011.10:g.119029311C>T NC_000011.9:g.118900021C>T NG_013331.1:g.6596G>A LRG_187:g.6596G>A LRG_187t1:c.59G>A LRG_187p1:p.Gly20Asp - Protein change
- G20D
- Other names
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- Canonical SPDI
- NC_000011.10:119029310: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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
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
Help
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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SLC37A4 | - | - |
GRCh38 GRCh38 GRCh37 |
998 | 1036 |
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
Help
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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Likely pathogenic (2) |
criteria provided, single submitter
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May 28, 2019 | RCV000059137.2 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000699431.8 | |
Pathogenic (1) |
criteria provided, single submitter
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May 12, 2022 | RCV002504976.1 |
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
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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 27, 2018)
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criteria provided, single submitter
Method: clinical testing
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Glucose-6-phosphate transport defect
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000920222.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: SLC37A4 c.59G>A (p.Gly20Asp) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. … (more)
Variant summary: SLC37A4 c.59G>A (p.Gly20Asp) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Two of two in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.4e-05 in 276916 control chromosomes (gnomAD). c.59G>A has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ib and Type Ic (Veiga-da-Cunha 1998, Galli 1999, Jun 2014). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Chen 2002). The most pronounced variant effect results in <10% of normal microsomal G6P uptake activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001135039.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Pathogenic
(May 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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Glucose-6-phosphate transport defect
Phosphate transport defect Congenital disorder of glycosylation, type IIw
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002807361.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Oct 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glucose-6-phosphate transport defect
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004202434.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Glucose-6-phosphate transport defect
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000828142.6
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 20 of the SLC37A4 protein … (more)
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 20 of the SLC37A4 protein (p.Gly20Asp). This variant is present in population databases (rs193302881, gnomAD 0.003%). This missense change has been observed in individual(s) with glycogen-storage disease type Ib (GSD Ib) (PMID: 9758626, 10518030, 12373566; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 68286). 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 SLC37A4 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SLC37A4 function (PMID: 12444104). For these reasons, this variant has been classified as Pathogenic. (less)
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
not provided
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UniProtKB/Swiss-Prot
Accession: SCV000090666.1
First in ClinVar: Oct 22, 2013 Last updated: Oct 22, 2013 |
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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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Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib. | Jun HS | Blood | 2014 | PMID: 24565827 |
Structure-function analysis of the glucose-6-phosphate transporter deficient in glycogen storage disease type Ib. | Chen LY | Human molecular genetics | 2002 | PMID: 12444104 |
Glycogen storage disease type I: diagnosis and phenotype/genotype correlation. | Matern D | European journal of pediatrics | 2002 | PMID: 12373566 |
Mutations in the glucose-6-phosphate transporter (G6PT) gene in patients with glycogen storage diseases type 1b and 1c. | Galli L | FEBS letters | 1999 | PMID: 10518030 |
A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. | Veiga-da-Cunha M | American journal of human genetics | 1998 | PMID: 9758626 |
Text-mined citations for rs193302881 ...
HelpRecord last updated Apr 15, 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.