ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.4046G>C (p.Gly1349Ala)

gnomAD frequency: 0.00005  dbSNP: rs151144102
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224490 SCV000280718 uncertain significance not provided 2015-12-21 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Invitae RCV000630902 SCV000751875 uncertain significance Fanconi anemia 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1349 of the SLX4 protein (p.Gly1349Ala). This variant is present in population databases (rs151144102, gnomAD 0.04%). This missense change has been observed in individual(s) with acute myeloid leukemia with myelodysplasia-related changes (PMID: 29146900). ClinVar contains an entry for this variant (Variation ID: 235267). 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 tolerated. 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 RCV000764055 SCV000895009 uncertain significance Fanconi anemia complementation group P 2021-07-09 criteria provided, single submitter clinical testing
GeneDx RCV000224490 SCV002004978 uncertain significance not provided 2020-01-27 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000224490 SCV002010079 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818545 SCV002070298 uncertain significance not specified 2020-10-26 criteria provided, single submitter clinical testing DNA sequence analysis of the SLX4 gene demonstrated a sequence change, c.4046G>C, in exon 12 which results in an amino acid change, p.Gly1349Ala. 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 frequency of 0.033% in the South Asian sub-population (dbSNP rs151144102). The p.Gly1349Ala change affects a poorly conserved amino acid residue located in a domain of the SLX4 protein that is not known to be functional. The p.Gly1349Ala substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to contrasting evidences and the lack of functional studies, the clinical significance of this sequence changes remains unknown at this time.
Sema4, Sema4 RCV000630902 SCV002529339 uncertain significance Fanconi anemia 2021-10-08 criteria provided, single submitter curation

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