Submissions for variant NM_139076.3(ABRAXAS1):c.577C>T (p.Arg193Ter)

gnomAD frequency: 0.00004  dbSNP: rs201698934

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587480	SCV000699906	uncertain significance	not provided	2017-01-19	criteria provided, single submitter	clinical testing	Variant summary: The FAM175A c.577C>T (p.Arg193X) variant results in a premature termination codon, predicted to cause a truncated or absent FAM175A protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Mutation predicts a damaging outcome for this substitution. This variant was found in 5/121352 control chromosomes at a frequency of 0.0000412, which is slightly exceeds the estimated maximal expected allele frequency of a pathogenic FAM175A variant (0.0000313), however, the allele frequencies in ExAC are calculated based on a very low number of occurrences (1-3 depending on the population studied), therefore they have to be taken with caution. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as variant of uncertain significance (VUS) until more information becomes available.
Invitae	RCV000587480	SCV001400063	uncertain significance	not provided	2022-07-04	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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 496539). This variant has not been reported in the literature in individuals affected with ABRAXAS1-related conditions. This variant is present in population databases (rs201698934, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg193*) in the ABRAXAS1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ABRAXAS1 cause disease.
CeGaT Center for Human Genetics Tuebingen	RCV000587480	SCV001502466	likely pathogenic	not provided	2020-10-01	criteria provided, single submitter	clinical testing