ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.1499C>T (p.Thr500Met)

gnomAD frequency: 0.00019  dbSNP: rs377440877
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000630881 SCV000751853 uncertain significance Fanconi anemia 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 500 of the SLX4 protein (p.Thr500Met). This variant is present in population databases (rs377440877, gnomAD 0.03%). This missense change has been observed in individual(s) with breast cancer (PMID: 30613976). ClinVar contains an entry for this variant (Variation ID: 526360). 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: "Deleterious"; 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.
Genetic Services Laboratory, University of Chicago RCV001821775 SCV002065437 uncertain significance not specified 2021-06-28 criteria provided, single submitter clinical testing DNA sequence analysis of the SLX4 gene demonstrated a sequence change, c.1499C>T, in exon 7 that results in an amino acid change, p.Thr500Met. This sequence change has been described in the gnomAD database with a frequency of 0.028% in the African/African American subpopulation (dbSNP rs377440877). The p.Thr500Met change affects a moderately 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.Thr500Met substitution. This sequence change does not appear to have been previously described in individuals with SLX4-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr500Met change remains unknown at this time.
Baylor Genetics RCV004568370 SCV005056876 uncertain significance Fanconi anemia complementation group P 2023-11-10 criteria provided, single submitter clinical testing

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