ClinVar Genomic variation as it relates to human health
NM_001164277.2(SLC37A4):c.652C>T (p.Gln218Ter)
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.652C>T (p.Gln218Ter)
Variation ID: 189147 Accession: VCV000189147.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q23.3 11: 119027069 (GRCh38) [ NCBI UCSC ] 11: 118897779 (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 20, 2024 Dec 8, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001164277.2:c.652C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001157749.1:p.Gln218Ter nonsense NM_001164278.2:c.652C>T NP_001157750.1:p.Gln218Ter nonsense NM_001164279.2:c.433C>T NP_001157751.1:p.Gln145Ter nonsense NM_001164280.2:c.652C>T NP_001157752.1:p.Gln218Ter nonsense NM_001467.6:c.652C>T NP_001458.1:p.Gln218Ter nonsense NC_000011.10:g.119027069G>A NC_000011.9:g.118897779G>A NG_013331.1:g.8837C>T LRG_187:g.8837C>T LRG_187t1:c.652C>T LRG_187p1:p.Gln218Ter - Protein change
- Q218*, Q145*
- Other names
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- Canonical SPDI
- NC_000011.10:119027068: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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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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SLC37A4 | - | - |
GRCh38 GRCh38 GRCh37 |
1008 | 1049 |
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
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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 8, 2022 | RCV000169570.7 |
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
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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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Likely pathogenic
(Aug 15, 2022)
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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: SCV002572042.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: SLC37A4 c.652C>T (p.Gln218X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: SLC37A4 c.652C>T (p.Gln218X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8.1e-06 in 247360 control chromosomes (gnomAD). c.652C>T has been reported in the literature in at least one compound heterozygous individual affected with Glycogen Storage Disease Type Ib (e.g. Veiga-da-Cunha_1998). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Both laboratories classified the variant as pathogenic (n=1) or likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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Pathogenic
(Dec 08, 2022)
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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: SCV004202487.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 19, 2021)
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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: SCV002235207.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189147). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189147). This premature translational stop signal has been observed in individual(s) with glycogen storage disease type Ib (PMID: 9758626). This variant is present in population databases (rs551439289, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln218*) 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). (less)
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Likely pathogenic
(Jan 22, 2015)
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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: SCV000221068.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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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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Pregnancy in glycogen storage disease type Ib: gestational care and report of first successful deliveries. | Dagli AI | Journal of inherited metabolic disease | 2010 | PMID: 20386986 |
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 |
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 rs551439289 ...
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.