rs192655642
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003356.4(UCP3):c.274G>A(p.Ala92Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,614,104 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 1 hom. )
Consequence
UCP3
NM_003356.4 missense
NM_003356.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 7.85
Genes affected
UCP3 (HGNC:12519): (uncoupling protein 3) Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. The different UCPs have tissue-specific expression; this gene is primarily expressed in skeletal muscle. This gene's protein product is postulated to protect mitochondria against lipid-induced oxidative stress. Expression levels of this gene increase when fatty acid supplies to mitochondria exceed their oxidation capacity and the protein enables the export of fatty acids from mitochondria. UCPs contain the three solcar protein domains typically found in MACPs. Two splice variants have been found for this gene.[provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18226075).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UCP3 | NM_003356.4 | c.274G>A | p.Ala92Thr | missense_variant | 3/7 | ENST00000314032.9 | |
UCP3 | NM_022803.3 | c.274G>A | p.Ala92Thr | missense_variant | 3/6 | ||
UCP3 | XM_047427519.1 | c.274G>A | p.Ala92Thr | missense_variant | 2/6 | ||
UCP3 | XR_007062495.1 | n.477G>A | non_coding_transcript_exon_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UCP3 | ENST00000314032.9 | c.274G>A | p.Ala92Thr | missense_variant | 3/7 | 1 | NM_003356.4 | P1 | |
UCP3 | ENST00000426995.2 | c.274G>A | p.Ala92Thr | missense_variant | 3/6 | 1 | |||
UCP3 | ENST00000544614.1 | c.274G>A | p.Ala92Thr | missense_variant | 2/2 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152216Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000140 AC: 35AN: 250544Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135568
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GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461770Hom.: 1 Cov.: 34 AF XY: 0.0000743 AC XY: 54AN XY: 727184
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74502
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 28, 2017 | - - |
Obesity Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 19, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;.
Polyphen
P;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at