Submissions for variant NM_000147.5(FUCA1):c.485G>A (p.Arg162Gln)

gnomAD frequency: 0.00001  dbSNP: rs372045495

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	RCV002271771	SCV002555700	uncertain significance	not specified	2022-06-07	criteria provided, single submitter	clinical testing	Variant summary: FUCA1 c.485G>A (p.Arg162Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 251484 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in FUCA1 causing Fucosidosis (4e-05 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.485G>A in individuals affected with Fucosidosis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003101537	SCV003242975	uncertain significance	Fucosidosis	2022-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 162 of the FUCA1 protein (p.Arg162Gln). This variant is present in population databases (rs372045495, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with FUCA1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FUCA1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics	RCV004047474	SCV004873837	uncertain significance	Inborn genetic diseases	2023-02-27	criteria provided, single submitter	clinical testing	The c.485G>A (p.R162Q) alteration is located in exon 2 (coding exon 2) of the FUCA1 gene. This alteration results from a G to A substitution at nucleotide position 485, causing the arginine (R) at amino acid position 162 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.