ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.1394C>T (p.Pro465Leu)

gnomAD frequency: 0.00024  dbSNP: rs372128800
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461464 SCV000547449 uncertain significance Fanconi anemia 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 465 of the SLX4 protein (p.Pro465Leu). This variant is present in population databases (rs372128800, gnomAD 0.05%). 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: 407909). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV000764063 SCV000895017 uncertain significance Fanconi anemia complementation group P 2018-10-31 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001821254 SCV002067125 uncertain significance not specified 2020-01-17 criteria provided, single submitter clinical testing DNA sequence analysis of the SLX4 gene demonstrated a sequence change, c.1394C>T, in exon 7 that results in an amino acid change, p.Pro465Leu. 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 population frequency of 0.053% in African subpopulations (dbSNP rs372128800). The p.Pro465Leu 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.Pro465Leu substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Pro465Leu change remains unknown at this time.
Sema4, Sema4 RCV000461464 SCV002529260 uncertain significance Fanconi anemia 2021-11-30 criteria provided, single submitter curation

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