Submissions for variant NM_032444.4(SLX4):c.1115G>A (p.Arg372Gln)

gnomAD frequency: 0.00003  dbSNP: rs372956623

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000291416	SCV000396886	uncertain significance	Fanconi anemia complementation group P	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001203848	SCV001375027	uncertain significance	Fanconi anemia	2022-10-12	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 372 of the SLX4 protein (p.Arg372Gln). This variant is present in population databases (rs372956623, gnomAD 0.04%). 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: 319180). 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003237824	SCV002010760	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000291416	SCV002813291	uncertain significance	Fanconi anemia complementation group P	2022-05-18	criteria provided, single submitter	clinical testing