rs144614070
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032444.4(SLX4):c.467C>T(p.Thr156Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 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. T156K) has been classified 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 | UniProt |
---|---|---|---|---|---|---|---|
SLX4 | NM_032444.4 | c.467C>T | p.Thr156Ile | missense_variant | 2/15 | ENST00000294008.4 | |
SLX4 | XM_024450471.2 | c.467C>T | p.Thr156Ile | missense_variant | 2/15 | ||
SLX4 | XM_011522715.4 | c.467C>T | p.Thr156Ile | missense_variant | 2/15 | ||
SLX4 | XR_007064923.1 | n.1116C>T | non_coding_transcript_exon_variant | 2/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLX4 | ENST00000294008.4 | c.467C>T | p.Thr156Ile | missense_variant | 2/15 | 5 | NM_032444.4 | P1 | |
SLX4 | ENST00000466154.5 | n.762C>T | non_coding_transcript_exon_variant | 1/7 | 1 | ||||
SLX4 | ENST00000486524.1 | n.1095C>T | non_coding_transcript_exon_variant | 2/4 | 2 | ||||
SLX4 | ENST00000697859.1 | n.1089C>T | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251496Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135922
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 07, 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1006307). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. This variant is present in population databases (rs144614070, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 156 of the SLX4 protein (p.Thr156Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at