ClinVar Genomic variation as it relates to human health
NM_001164277.2(SLC37A4):c.742C>T (p.Gln248Ter)
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.742C>T (p.Gln248Ter)
Variation ID: 188762 Accession: VCV000188762.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q23.3 11: 119026979 (GRCh38) [ NCBI UCSC ] 11: 118897689 (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 Mar 29, 2015 Feb 14, 2024 Oct 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001164277.2:c.742C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001157749.1:p.Gln248Ter nonsense NM_001164278.2:c.742C>T NP_001157750.1:p.Gln248Ter nonsense NM_001164279.2:c.523C>T NP_001157751.1:p.Gln175Ter nonsense NM_001164280.2:c.742C>T NP_001157752.1:p.Gln248Ter nonsense NM_001467.6:c.742C>T NP_001458.1:p.Gln248Ter nonsense NC_000011.10:g.119026979G>A NC_000011.9:g.118897689G>A NG_013331.1:g.8927C>T LRG_187:g.8927C>T LRG_187t1:c.742C>T LRG_187p1:p.Gln248Ter - Protein change
- Q248*, Q175*
- Other names
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- Canonical SPDI
- NC_000011.10:119026978:G:A
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
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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SLC37A4 | - | - |
GRCh38 GRCh38 GRCh37 |
998 | 1036 |
Conditions - Germline
Condition
Help
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
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
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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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Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Oct 28, 2023 | RCV000169082.10 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 9, 2023 | RCV000300702.3 |
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
(Jul 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glucose-6-phosphate transport defect
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004099023.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
PVS1, PM2, PM3
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Pathogenic
(Sep 19, 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: SCV004202445.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Mar 09, 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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Revvity Omics, Revvity
Accession: SCV004238361.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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Pathogenic
(Oct 28, 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:
germline
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Invitae
Accession: SCV000949803.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln248*) in the SLC37A4 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln248*) in the SLC37A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC37A4 are known to be pathogenic (PMID: 9758626, 10940311). This variant is present in population databases (rs781784543, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with glycogen storage disease type Ib (PMID: 9758626, 10026167, 18437526). ClinVar contains an entry for this variant (Variation ID: 188762). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 28, 2016)
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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: SCV000697757.1
First in ClinVar: Mar 29, 2015 Last updated: Mar 29, 2015 |
Comment:
Variant summary: The SLC37A4 c.742C>T (p.Gln248X) variant results in a premature termination codon, predicted to cause a truncated or absent SLC37A4 protein due to nonsense … (more)
Variant summary: The SLC37A4 c.742C>T (p.Gln248X) variant results in a premature termination codon, predicted to cause a truncated or absent SLC37A4 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 2/118148 control chromosomes at a frequency of 0.0000169, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC37A4 variant (0.0012247). This variant has been reported in multiple GSD type 1b patients both homozygously and heterozygously. In addition, one clinical diagnostic laboratory classified this variant as likely pathogenic, without evidence to independently evaluate. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Jul 20, 2018)
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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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GeneDx
Accession: SCV000330663.5
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
The Q248X pathogenic variant in the SLC37A4 gene has been reported previously in association with glycogen storage disease type 1b when present in the homozygous … (more)
The Q248X pathogenic variant in the SLC37A4 gene has been reported previously in association with glycogen storage disease type 1b when present in the homozygous state or when in trans with another pathogenic variant (Veiga-da-Cunha et al., 1998; Melis et al., 2005; Jun et al., 2014). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q248X variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Q248X as a pathogenic variant. (less)
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Likely pathogenic
(Apr 21, 2014)
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criteria provided, single submitter
Method: literature only
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Glucose-6-phosphate transport defect
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220256.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Glycogen storage disease type Ib
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001457665.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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 |
Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders? | Melis D | Journal of inherited metabolic disease | 2008 | PMID: 18437526 |
Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature. | Melis D | European journal of pediatrics | 2005 | PMID: 15906092 |
Glycogen storage disease type I: diagnosis and phenotype/genotype correlation. | Matern D | European journal of pediatrics | 2002 | PMID: 12373566 |
Structural requirements for the stability and microsomal transport activity of the human glucose 6-phosphate transporter. | Chen LY | The Journal of biological chemistry | 2000 | PMID: 10940311 |
Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b. | Hiraiwa H | The Journal of biological chemistry | 1999 | PMID: 10026167 |
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 rs781784543 ...
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.