ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.4546G>A (p.Gly1516Arg)

gnomAD frequency: 0.00001  dbSNP: rs775915651
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001094465 SCV000396826 uncertain significance Fanconi anemia complementation group P 2018-01-13 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 RCV000284703 SCV001199423 uncertain significance Fanconi anemia 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1516 of the SLX4 protein (p.Gly1516Arg). This variant is present in population databases (rs775915651, gnomAD 0.004%). 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: 319151). 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.
Fulgent Genetics, Fulgent Genetics RCV001094465 SCV002793582 uncertain significance Fanconi anemia complementation group P 2021-11-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002522846 SCV003548414 uncertain significance Inborn genetic diseases 2022-10-25 criteria provided, single submitter clinical testing The c.4546G>A (p.G1516R) alteration is located in exon 12 (coding exon 11) of the SLX4 gene. This alteration results from a G to A substitution at nucleotide position 4546, causing the glycine (G) at amino acid position 1516 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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