Submissions for variant NM_139076.3(ABRAXAS1):c.364C>G (p.Gln122Glu)

dbSNP: rs137876115

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000590602	SCV000150098	uncertain significance	not provided	2014-03-03	criteria provided, single submitter	clinical testing	FAM175A has only recently been described in association with cancer predisposition and the risks are not well understood. This variant is denoted FAM175A c.364C>G at the cDNA level, p.Gln122Glu (Q122E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAG>GAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FAM175A Gln122Glu was observed with an allele frequency of 0.2% in Africans in 1000 Genomes and 0.7% in African Americans in the NHLBI Exome Sequencing Project. Since Glutamine and Glutamic Acid differ in some properties, this is considered a semi-conservative amino acid substitution and may affect secondary protein structure. FAM175A Gln122Glu occurs at a position that is highly conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the FAM175A gene, remain unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000590602	SCV000562566	benign	not provided	2024-01-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590602	SCV000699902	likely benign	not provided	2017-01-16	criteria provided, single submitter	clinical testing	Variant summary: The FAM175A c.364C>G (p.Gln122Glu) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 56/123538 control chromosomes at a frequency of 0.0004533, which is approximately 15 times the estimated maximal expected allele frequency of a pathogenic FAM175A variant (0.0000313), suggesting this variant is likely a benign polymorphism. This variant has been reported in three patients with early onset breast cancer without strong evidence supporting its pathogenicity (Renault_2016). In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. Taken together, this variant is classified as likely benign.