ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.1493C>T (p.Ser498Phe)

gnomAD frequency: 0.00001  dbSNP: rs1326014010
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001820629 SCV002068060 uncertain significance not specified 2021-09-21 criteria provided, single submitter clinical testing This sequence change does not appear to have been previously described in patients with SLX4-related disorders and has been described in the gnomAD database with a low population frequency of 0.00040% (dbSNP rs1326014010). The p.Ser498Phe change affects a poorly conserved amino acid residue located in a domain of the SLX4 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ser498Phe substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Ser498Phe change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869730 SCV002197294 uncertain significance Fanconi anemia 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 498 of the SLX4 protein (p.Ser498Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics RCV002478059 SCV002793931 uncertain significance Fanconi anemia complementation group P 2022-05-19 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.