rs181782315
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_032444.4(SLX4):c.4765C>T(p.Arg1589Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,614,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1589H) has been classified as Uncertain significance.
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.4765C>T | p.Arg1589Cys | missense_variant | 14/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.4765C>T | p.Arg1589Cys | missense_variant | 14/15 | ||
SLX4 | XM_011522715.4 | c.4762C>T | p.Arg1588Cys | missense_variant | 14/15 | ||
SLX4 | XM_047434801.1 | c.3763C>T | p.Arg1255Cys | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.4765C>T | p.Arg1589Cys | missense_variant | 14/15 | 5 | NM_032444.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000159 AC: 40AN: 251396Hom.: 1 AF XY: 0.000155 AC XY: 21AN XY: 135890
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461848Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 727230
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74494
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1589 of the SLX4 protein (p.Arg1589Cys). This variant is present in population databases (rs181782315, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. 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: 456329). 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. - |
Fanconi anemia complementation group P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 20, 2021 | - - |
SLX4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 14, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at