ClinVar Miner

Submissions for variant NM_001126108.2(SLC12A3):c.2721-1G>A

gnomAD frequency: 0.00002  dbSNP: rs761242621
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000806887 SCV000946908 likely pathogenic not provided 2023-12-28 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 23 of the SLC12A3 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 SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442). This variant is present in population databases (rs761242621, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC12A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 651512). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Centogene AG - the Rare Disease Company RCV001276383 SCV002059859 likely pathogenic Familial hypokalemia-hypomagnesemia 2020-07-23 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001276383 SCV002816087 likely pathogenic Familial hypokalemia-hypomagnesemia 2021-11-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV002537234 SCV003595235 likely pathogenic Inborn genetic diseases 2021-12-08 criteria provided, single submitter clinical testing The c.2748-1G>A intronic variant results from a G to A substitution one nucleotide before coding exon 24 of the SLC12A3 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on data from gnomAD, the A allele has an overall frequency of <0.01% (6/251446) total alleles studied. The highest observed frequency was 0.02% (6/34592) of Latino alleles. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Based on the available evidence, this alteration is classified as likely pathogenic.
Natera, Inc. RCV001276383 SCV001462631 likely pathogenic Familial hypokalemia-hypomagnesemia 2020-09-16 no assertion criteria provided clinical testing

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