ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.2521+255G>A

gnomAD frequency: 0.00007  dbSNP: rs1037430183
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
European Hospital Georges Pompidou Genetics Department, Assistance Publique - Hôpitaux de Paris AP-HP RCV002245171 SCV002513841 likely pathogenic Familial hypokalemia-hypomagnesemia 2022-04-27 criteria provided, single submitter clinical testing ACMG criteria used:PS3, PM2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587331 SCV005076207 uncertain significance not specified 2024-04-15 criteria provided, single submitter clinical testing Variant summary: SLC12A3 c.2548+255G>A is located at a position not widely known to affect splicing. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a cryptic 5' donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing, reporting inclusion of a 90-bp pseudoexon in intron 21 detected by midigene splicing assay (e.g. Viering_2023). The frequency of this variant in the general population could not be determined as the technology used for large population databases (ExAC, gnomAD, ESP, 1000G) cannot detect variants of this type. c.2548+255G>A has been reported in the literature in at least one compound heterozygous individual affected with Gitelman syndrome (e.g. Viering_2023). This report does not provide unequivocal conclusions about association of the variant with Familial Hypokalemia-Hypomagnesemia. The following publication has been ascertained in the context of this evaluation (PMID: 36302598). ClinVar contains an entry for this variant (Variation ID: 1684172). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002245171 SCV005640174 likely pathogenic Familial hypokalemia-hypomagnesemia 2024-04-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003933708 SCV004762329 likely benign SLC12A3-related disorder 2019-11-12 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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