ClinVar Miner

Submissions for variant NM_139076.3(ABRAXAS1):c.332C>T (p.Thr111Met)

gnomAD frequency: 0.00001  dbSNP: rs1553936765
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Total submissions: 3
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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 RCV004024689 SCV000699869 uncertain significance not specified 2025-02-10 criteria provided, single submitter clinical testing Variant summary: FAM175A (ABRAXAS1) c.332C>T (p.Thr111Met) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251184 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.332C>T has been reported in the literature in an individual affected with breast cancer as well as an unaffected control (Dorling_2021). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. 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: 33471991). ClinVar contains an entry for this variant (Variation ID: 496522). Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000588056 SCV001213883 uncertain significance not provided 2019-12-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ABRAXAS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 496522). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with methionine at codon 111 of the ABRAXAS1 protein (p.Thr111Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine.
Ambry Genetics RCV004024689 SCV002754613 uncertain significance not specified 2024-02-13 criteria provided, single submitter clinical testing The p.T111M variant (also known as c.332C>T), located in coding exon 5 of the FAM175A gene, results from a C to T substitution at nucleotide position 332. The threonine at codon 111 is replaced by methionine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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