chr11-74001506-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 (★). 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, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2022 | 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 (http://gnomad.broadinstitute.org/variant/11-73712551-C-T). At this time, the clinical significance of this 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