ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.5423T>G (p.Phe1808Cys)

gnomAD frequency: 0.00002  dbSNP: rs371390105
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001220329 SCV001392309 uncertain significance Fanconi anemia 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 1808 of the SLX4 protein (p.Phe1808Cys). This variant is present in population databases (rs371390105, gnomAD 0.002%). 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: 948967). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.
Genetic Services Laboratory, University of Chicago RCV001819911 SCV002069968 uncertain significance not specified 2019-12-16 criteria provided, single submitter clinical testing DNA sequence analysis of the SLX4 gene demonstrated a sequence change, c.5423T>G, in exon 15 that results in an amino acid change, p.Phe1808Cys. 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 0.0023% in non-Finnish European subpopulation (dbSNP rs371390105). The p.Phe1808Cys change affects a highly conserved amino acid residue located in a domain of the SLX4 protein that is not known to be functional. The p.Phe1808Cys substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these evidences and the lack of functional studies, the clinical significance of the p.Phe1808Cys change remains unknown at this time.

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