Submissions for variant NM_032444.4(SLX4):c.4765C>T (p.Arg1589Cys)

gnomAD frequency: 0.00004  dbSNP: rs181782315

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000528694	SCV000626442	uncertain significance	Fanconi anemia	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1589 of the SLX4 protein (p.Arg1589Cys). This variant is present in population databases (rs181782315, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with SLX4-related conditions. ClinVar contains an entry for this variant (Variation ID: 456329). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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	RCV000765293	SCV000896548	uncertain significance	Fanconi anemia complementation group P	2021-10-20	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925584	SCV004740607	likely benign	SLX4-related condition	2023-07-14	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).