Submissions for variant NM_139076.3(ABRAXAS1):c.33G>C (p.Ser11=)

gnomAD frequency: 0.00036  dbSNP: rs368088450

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000160465	SCV000211030	benign	not specified	2014-01-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000590492	SCV000291356	benign	not provided	2024-01-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590492	SCV000699899	benign	not provided	2016-05-20	criteria provided, single submitter	clinical testing	Variant summary: The FAM175A c.33G>C (p.Ser11Ser) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing. The variant of interest was observed in the large and broad control populations of ExAC with an allele frequency of 75/112322 control chromosomes (1 homozygote, 1/1497, frequency: 0.0006677), predominantly in the East Asian cohort (1 homozygote, 1/119, frequency: 0.008 (70/8348)), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic FAM175A variant of 1/31948 (0.0000313). This suggests that the variant is a polymorphism found mainly in population(s) of East Asian origin. The variant of interest, to our knowledge, has not been reported in affected individuals via publications, although an internal LCA sample reports the variant to co-occur with a pathogenic BRCA1 variant p.Gln563X. In addition, a clinical laboratory also cites the variant in ClinVar as "benign." Therefore, taken all available lines of evidence into consideration, the variant of interest is classified as Benign.
Ambry Genetics	RCV000160465	SCV002755472	likely benign	not specified	2022-02-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003937477	SCV004751687	benign	ABRAXAS1-related disorder	2019-05-24	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).