rs765960272
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_032444.4(SLX4):āc.5060C>Gā(p.Pro1687Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,614,240 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.5060C>G | p.Pro1687Arg | missense_variant | 14/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.5060C>G | p.Pro1687Arg | missense_variant | 14/15 | ||
SLX4 | XM_011522715.4 | c.5057C>G | p.Pro1686Arg | missense_variant | 14/15 | ||
SLX4 | XM_047434801.1 | c.4058C>G | p.Pro1353Arg | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.5060C>G | p.Pro1687Arg | missense_variant | 14/15 | 5 | NM_032444.4 | P1 | |
ENST00000573982.1 | n.253G>C | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000147 AC: 37AN: 251492Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135920
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461890Hom.: 1 Cov.: 33 AF XY: 0.0000701 AC XY: 51AN XY: 727246
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74500
ClinVar
Submissions by phenotype
Fanconi anemia complementation group P Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 29, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1687 of the SLX4 protein (p.Pro1687Arg). This variant is present in population databases (rs765960272, gnomAD 0.1%). 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: 319144). 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 disruptive. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 20, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Classified as a variant of uncertain significance in a Korean patient with clinical features indicative of hereditary breast cancer (Park et al., 2018); specific variant information provided by Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 29338689) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at