ClinVar Miner

Submissions for variant NM_001164277.2(SLC37A4):c.1124+2dup

gnomAD frequency: 0.00001  dbSNP: rs1459811938
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987704 SCV000920219 uncertain significance not specified 2024-01-11 criteria provided, single submitter clinical testing Variant summary: SLC37A4 c.1123+2dupT alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 247958 control chromosomes (gnomAD). c.1123+2dupT has been reported in the literature in individuals affected with Glycogen Storage Disease Type Ib (Halligan_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 33977030). ClinVar contains an entry for this variant (Variation ID: 633416). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000781848 SCV002285400 uncertain significance Glucose-6-phosphate transport defect 2021-02-18 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the SLC37A4 gene. It does not directly change the encoded amino acid sequence of the SLC37A4 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SLC37A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 633416). Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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