rs201205533
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_001371395.1(USP53):c.173G>A(p.Arg58Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,654 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001371395.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USP53 | NM_001371395.1 | c.173G>A | p.Arg58Gln | missense_variant | Exon 6 of 19 | ENST00000692078.1 | NP_001358324.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000717 AC: 109AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000465 AC: 116AN: 249334Hom.: 0 AF XY: 0.000436 AC XY: 59AN XY: 135270
GnomAD4 exome AF: 0.00107 AC: 1562AN: 1461548Hom.: 1 Cov.: 30 AF XY: 0.00105 AC XY: 763AN XY: 727080
GnomAD4 genome AF: 0.000717 AC: 109AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.000565 AC XY: 42AN XY: 74296
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 58 of the USP53 protein (p.Arg58Gln). This variant is present in population databases (rs201205533, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with USP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 619050). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt USP53 protein function with a positive predictive value of 80%. 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. -
Premature ovarian insufficiency Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at