Submissions for variant NM_032444.4(SLX4):c.4384G>T (p.Ala1462Ser)

gnomAD frequency: 0.00034  dbSNP: rs138484365

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000504033	SCV000597134	uncertain significance	not specified	2016-03-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764052	SCV000895006	uncertain significance	Fanconi anemia complementation group P	2022-04-12	criteria provided, single submitter	clinical testing
Invitae	RCV001203560	SCV001374733	uncertain significance	Fanconi anemia	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1462 of the SLX4 protein (p.Ala1462Ser). This variant is present in population databases (rs138484365, gnomAD 0.04%). 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: 436778). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine 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.
Baylor Genetics	RCV000764052	SCV002096988	uncertain significance	Fanconi anemia complementation group P	2022-01-11	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Sema4, Sema4	RCV001203560	SCV002529351	uncertain significance	Fanconi anemia	2021-10-21	criteria provided, single submitter	curation
Ambry Genetics	RCV002524298	SCV003615531	uncertain significance	Inborn genetic diseases	2022-01-07	criteria provided, single submitter	clinical testing	The c.4384G>T (p.A1462S) alteration is located in exon 12 (coding exon 11) of the SLX4 gene. This alteration results from a G to T substitution at nucleotide position 4384, causing the alanine (A) at amino acid position 1462 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.