This sequence change affects a donor splice site in intron 9 of the SLC37A4 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of autosomal recessive SLC37A4-related conditions and/or glycogen storage disease type I (PMID: 10482875, 11071391, 16716283; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS8+1G>C. ClinVar contains an entry for this variant (Variation ID: 583102). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001164277.2(SLC37A4):c.1124+1G>C
Germline
Classification
Help
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.
(2)
Help
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.
Pathogenic
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001164277.2(SLC37A4):c.1124+1G>C
Variation ID: 583102 Accession: VCV000583102.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q23.3 11: 119025190 (GRCh38) [ NCBI UCSC ] 11: 118895900 (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 10, 2018 Jul 23, 2024 Oct 26, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001164277.2:c.1124+1G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001164278.2:c.1190+1G>C splice donor NM_001164279.2:c.905+1G>C splice donor NM_001164280.2:c.1124+1G>C splice donor NM_001467.6:c.1124+1G>C splice donor NC_000011.10:g.119025190C>G NC_000011.9:g.118895900C>G NG_013331.1:g.10716G>C LRG_187:g.10716G>C LRG_187t1:c.1123+1G>C - Protein change
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- Other names
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- Canonical SPDI
- NC_000011.10:119025189:C: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.
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- 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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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 |
1010 | 1051 | |
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. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 26, 2023 | RCV000707348.9 |
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
(Oct 26, 2023)
|
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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000836440.5
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects a donor splice site in intron 9 of the SLC37A4 gene. While this variant is not anticipated to result in nonsense … (more)
This sequence change affects a donor splice site in intron 9 of the SLC37A4 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of autosomal recessive SLC37A4-related conditions and/or glycogen storage disease type I (PMID: 10482875, 11071391, 16716283; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS8+1G>C. ClinVar contains an entry for this variant (Variation ID: 583102). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
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Pathogenic
(Feb 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Glucose-6-phosphate transport defect
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002557749.2
First in ClinVar: Aug 08, 2022 Last updated: Jul 23, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with glycogen storage disease type Ib (GSD Ib) (MIM#232220). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0701 - Other canonical splice variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Four different variants in the same splice junction have previously been reported, sometimes in an alternate transcript using different nomenclature, in at least five individuals with GSD Ib (MIM#232220) (HGMD, PMIDs: 10482875, 11071391, 15906092, 33977030). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported in a compound heterozygous state, sometimes in an alternate transcript using different nomenclature, in three individuals with GSD Ib (MIM#232220) (HGMD, PMIDs: 16716283, 25881301, 29549044). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (external testing by Invitae). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
Comment:
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with glycogen storage disease type Ib (GSD Ib) (MIM#232220). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0701 - Other canonical splice variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Four different variants in the same splice junction have previously been reported, sometimes in an alternate transcript using different nomenclature, in at least five individuals with GSD Ib (MIM#232220) (HGMD, PMIDs: 10482875, 11071391, 15906092, 33977030). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported in a compound heterozygous state, sometimes in an alternate transcript using different nomenclature, in three individuals with GSD Ib (MIM#232220) (HGMD, PMIDs: 16716283, 25881301, 29549044). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (external testing by Invitae). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
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. |
Comment:
This sequence change affects a donor splice site in intron 9 of the SLC37A4 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of autosomal recessive SLC37A4-related conditions and/or glycogen storage disease type I (PMID: 10482875, 11071391, 16716283; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS8+1G>C. ClinVar contains an entry for this variant (Variation ID: 583102). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with glycogen storage disease type Ib (GSD Ib) (MIM#232220). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0701 - Other canonical splice variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Four different variants in the same splice junction have previously been reported, sometimes in an alternate transcript using different nomenclature, in at least five individuals with GSD Ib (MIM#232220) (HGMD, PMIDs: 10482875, 11071391, 15906092, 33977030). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported in a compound heterozygous state, sometimes in an alternate transcript using different nomenclature, in three individuals with GSD Ib (MIM#232220) (HGMD, PMIDs: 16716283, 25881301, 29549044). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (external testing by Invitae). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| The natural history of glycogen storage disease type Ib in England: A multisite survey. | Halligan R | JIMD reports | 2021 | PMID: 33977030 |
| Unexpected Findings in a Patient With Hepatomegaly and Skin Rashes. | Bai J | Gastroenterology | 2018 | PMID: 29549044 |
| Inflammatory bowel disease (IBD)-like disease in a case of a 33-year old man with glycogenosis 1b. | Volz MS | BMC gastroenterology | 2015 | PMID: 25881301 |
| Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
| Resequencing the G6PT1 gene reveals a novel splicing mutation in a patient with glycogen storage disease type 1b. | Lam CW | Clinica chimica acta; international journal of clinical chemistry | 2006 | PMID: 16716283 |
| 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 |
| Mutation analysis in glycogen storage disease type 1 non-a. | Janecke AR | Human genetics | 2000 | PMID: 11071391 |
| Glycogen storage disease type Ib: structural and mutational analysis of the microsomal glucose-6-phosphate transporter gene. | Hou DC | American journal of medical genetics | 1999 | PMID: 10482875 |
| Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Text-mined citations for rs782630676 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 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.