11-74001506-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_003356.4(UCP3):c.845G>A(p.Arg282His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,814 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 (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R282C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003356.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UCP3 | NM_003356.4 | c.845G>A | p.Arg282His | missense_variant | 7/7 | ENST00000314032.9 | |
UCP3 | XM_047427519.1 | c.845G>A | p.Arg282His | missense_variant | 6/6 | ||
UCP3 | XR_007062495.1 | n.3135G>A | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UCP3 | ENST00000314032.9 | c.845G>A | p.Arg282His | missense_variant | 7/7 | 1 | NM_003356.4 | P1 | |
UCP3 | ENST00000545271.1 | n.536G>A | non_coding_transcript_exon_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151974Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251472Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461840Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727228
GnomAD4 genome AF: 0.0000197 AC: 3AN: 151974Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74212
ClinVar
Submissions by phenotype
UCP3-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 21, 2024 | The UCP3 c.845G>A variant is predicted to result in the amino acid substitution p.Arg282His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD. Alternative variant at the same codon p.Arg282Cys has been reported in both lean and obese individuals in an obesity study (Chung et al. 1999. PubMed ID: 10480626) and the functional study showed that this variant affects UCP3 function (Hagen et al. 1999. PubMed ID: 10431807). At this time, the clinical significance of p.Arg282His variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at