Submissions for variant NM_001312909.2(FAM111A):c.1477C>T (p.Arg493Ter)

dbSNP: rs761191576

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002577774	SCV002946292	benign	not provided	2024-06-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003331375	SCV004039379	uncertain significance	not specified	2023-08-24	criteria provided, single submitter	clinical testing	Variant summary: FAM111A c.1477C>T (p.Arg493X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, however the molecular mechanism of disease attributed to FAM111A is gain-of-function. The variant allele was found at a frequency of 7.6e-05 in 251020 control chromosomes in the gnomAD database, including 1 homozygotes. To our knowledge, no occurrence of c.1477C>T in individuals affected with Autosomal Dominant Kenny-Caffey Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.