rs181942292
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032444.4(SLX4):c.973A>T(p.Thr325Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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 Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.973A>T | p.Thr325Ser | missense_variant | 5/15 | ENST00000294008.4 | NP_115820.2 | |
SLX4 | XM_024450471.2 | c.973A>T | p.Thr325Ser | missense_variant | 5/15 | XP_024306239.1 | ||
SLX4 | XM_011522715.4 | c.973A>T | p.Thr325Ser | missense_variant | 5/15 | XP_011521017.1 | ||
SLX4 | XR_007064923.1 | n.1622A>T | non_coding_transcript_exon_variant | 5/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.973A>T | p.Thr325Ser | missense_variant | 5/15 | 5 | NM_032444.4 | ENSP00000294008 | P1 | |
SLX4 | ENST00000466154.5 | n.2194A>T | non_coding_transcript_exon_variant | 3/7 | 1 | |||||
SLX4 | ENST00000486524.1 | n.2527A>T | non_coding_transcript_exon_variant | 4/4 | 2 | |||||
SLX4 | ENST00000697858.1 | n.314A>T | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251190Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135806
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727200
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74450
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 325 of the SLX4 protein (p.Thr325Ser). This variant is present in population databases (rs181942292, gnomAD 0.09%). 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: 407921). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at