chr11-125893982-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_031307.4(PUS3):c.1249C>T(p.Arg417Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R417H) has been classified as Uncertain significance.
Frequency
Consequence
NM_031307.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PUS3 | NM_031307.4 | c.1249C>T | p.Arg417Cys | missense_variant | 4/4 | ENST00000227474.8 | |
HYLS1 | NM_001134793.2 | c.-26+2510G>A | intron_variant | ENST00000425380.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PUS3 | ENST00000227474.8 | c.1249C>T | p.Arg417Cys | missense_variant | 4/4 | 1 | NM_031307.4 | P1 | |
HYLS1 | ENST00000425380.7 | c.-26+2510G>A | intron_variant | 3 | NM_001134793.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251432Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135902
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 727236
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 20, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 417 of the PUS3 protein (p.Arg417Cys). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with PUS3-related conditions. This variant is present in population databases (rs767221951, gnomAD 0.02%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at