rs1060501798
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032444.4(SLX4):c.802G>A(p.Val268Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★★).
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.802G>A | p.Val268Met | missense_variant | 4/15 | ENST00000294008.4 | NP_115820.2 | |
SLX4 | XM_024450471.2 | c.802G>A | p.Val268Met | missense_variant | 4/15 | XP_024306239.1 | ||
SLX4 | XM_011522715.4 | c.802G>A | p.Val268Met | missense_variant | 4/15 | XP_011521017.1 | ||
SLX4 | XR_007064923.1 | n.1451G>A | non_coding_transcript_exon_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.802G>A | p.Val268Met | missense_variant | 4/15 | 5 | NM_032444.4 | ENSP00000294008.3 | ||
SLX4 | ENST00000466154.5 | n.1097G>A | non_coding_transcript_exon_variant | 3/7 | 1 | |||||
SLX4 | ENST00000486524.1 | n.1430G>A | non_coding_transcript_exon_variant | 4/4 | 2 | |||||
SLX4 | ENST00000697858.1 | n.143G>A | non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251420Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135900
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727204
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 04, 2022 | The c.802G>A (p.V268M) alteration is located in exon 4 (coding exon 3) of the SLX4 gene. This alteration results from a G to A substitution at nucleotide position 802, causing the valine (V) at amino acid position 268 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 01, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 407937). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 268 of the SLX4 protein (p.Val268Met). - |
Fanconi anemia complementation group P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 30, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at