ClinVar Miner

Submissions for variant NM_139076.3(ABRAXAS1):c.1056T>G (p.Asp352Glu)

gnomAD frequency: 0.00029  dbSNP: rs773812911
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791356 SCV000266772 uncertain significance not provided 2023-09-27 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 224927). This variant has not been reported in the literature in individuals affected with ABRAXAS1-related conditions. This variant is present in population databases (rs773812911, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 352 of the ABRAXAS1 protein (p.Asp352Glu). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000210492 SCV000917323 likely benign not specified 2021-03-13 criteria provided, single submitter clinical testing Variant summary: FAM175A/ABRAXAS1 c.1056T>G (p.Asp352Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 251338 control chromosomes, predominantly at a frequency of 0.00066 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 21 fold of the estimated maximal expected allele frequency for a pathogenic variant in FAM175A causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (3.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.1056T>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics RCV003165519 SCV003860189 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-25 criteria provided, single submitter clinical testing The p.D352E variant (also known as c.1056T>G), located in coding exon 9 of the FAM175A gene, results from a T to G substitution at nucleotide position 1056. The aspartic acid at codon 352 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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