ClinVar Miner

Submissions for variant NM_001164277.2(SLC37A4):c.381+2T>G

gnomAD frequency: 0.00001  dbSNP: rs782645078
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Total submissions: 4
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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 RCV000781850 SCV000920221 likely pathogenic Glucose-6-phosphate transport defect 2018-05-21 criteria provided, single submitter clinical testing Variant summary: SLC37A4 c.381+2T>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.2e-05 in 30900 control chromosomes (gnomAD). To our knowledge, no occurrence of c.381+2T>G in individuals affected with Glycogen Storage Disease Type Ib and no experimental evidence demonstrating its impact on protein function have been reported. 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 likely pathogenic
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268012 SCV001446588 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV000781850 SCV004202491 pathogenic Glucose-6-phosphate transport defect 2022-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000781850 SCV004538990 pathogenic Glucose-6-phosphate transport defect 2023-10-25 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the SLC37A4 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC37A4 are known to be pathogenic (PMID: 9758626, 10940311). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with autosomal recessive glycogen storage disease type Ib (PMID: 10482962). 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 c.550+2(T‚ÜíG) . ClinVar contains an entry for this variant (Variation ID: 633418). 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.

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