rs750475726
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032444.4(SLX4):c.806C>T(p.Ala269Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A269S) has been classified as Uncertain significance.
Frequency
Consequence
NM_032444.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.806C>T | p.Ala269Val | missense_variant | 4/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.806C>T | p.Ala269Val | missense_variant | 4/15 | ||
SLX4 | XM_011522715.4 | c.806C>T | p.Ala269Val | missense_variant | 4/15 | ||
SLX4 | XR_007064923.1 | n.1455C>T | non_coding_transcript_exon_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.806C>T | p.Ala269Val | missense_variant | 4/15 | 5 | NM_032444.4 | P1 | |
SLX4 | ENST00000466154.5 | n.1101C>T | non_coding_transcript_exon_variant | 3/7 | 1 | ||||
SLX4 | ENST00000486524.1 | n.1434C>T | non_coding_transcript_exon_variant | 4/4 | 2 | ||||
SLX4 | ENST00000697858.1 | n.147C>T | non_coding_transcript_exon_variant | 2/3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251416Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135898
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461806Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727198
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 269 of the SLX4 protein (p.Ala269Val). This variant is present in population databases (rs750475726, gnomAD 0.002%). 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: 241700). 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: "Deleterious"; 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at