Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000972904 | SCV001120634 | benign | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782616 | SCV005395465 | uncertain significance | not specified | 2024-09-18 | criteria provided, single submitter | clinical testing | Variant summary: SLC12A3 c.966G>A (p.Ala322Ala) 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: Two predict the variant weakens a 3' acceptor site. Three predict the variant creates a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00017 in 251446 control chromosomes, predominantly at a frequency of 0.0021 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in SLC12A3 causing Familial Hypokalemia-Hypomagnesemia, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.966G>A in individuals affected with Familial Hypokalemia-Hypomagnesemia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 790165). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV001274423 | SCV001458554 | uncertain significance | Familial hypokalemia-hypomagnesemia | 2020-03-10 | no assertion criteria provided | clinical testing |