11-74001507-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003356.4(UCP3):c.844C>T(p.Arg282Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,613,864 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. R282H) has been classified as Uncertain significance.
Frequency
Consequence
NM_003356.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UCP3 | NM_003356.4 | c.844C>T | p.Arg282Cys | missense_variant | 7/7 | ENST00000314032.9 | |
UCP3 | XM_047427519.1 | c.844C>T | p.Arg282Cys | missense_variant | 6/6 | ||
UCP3 | XR_007062495.1 | n.3134C>T | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UCP3 | ENST00000314032.9 | c.844C>T | p.Arg282Cys | missense_variant | 7/7 | 1 | NM_003356.4 | P1 | |
UCP3 | ENST00000545271.1 | n.535C>T | non_coding_transcript_exon_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000922 AC: 14AN: 151924Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000111 AC: 28AN: 251462Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135912
GnomAD4 exome AF: 0.0000841 AC: 123AN: 1461822Hom.: 0 Cov.: 30 AF XY: 0.0000825 AC XY: 60AN XY: 727216
GnomAD4 genome ? AF: 0.0000921 AC: 14AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | ClinVar contains an entry for this variant (Variation ID: 2181152). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 282 of the UCP3 protein (p.Arg282Cys). This variant is present in population databases (rs8179179, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with obesity (PMID: 10480626). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt UCP3 protein function. Experimental studies have shown that this missense change affects UCP3 function (PMID: 10431807). 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