GeneBe

rs1685356

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003356.4(UCP3):​c.825-288A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

UCP3
NM_003356.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.468

Publications

15 publications found
Variant links:
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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UCP3NM_003356.4 linkc.825-288A>T intron_variant Intron 6 of 6 ENST00000314032.9 NP_003347.1 P55916-1A0A0S2Z4G5
UCP3XR_007062495.1 linkn.3040A>T non_coding_transcript_exon_variant Exon 6 of 7
UCP3XM_047427519.1 linkc.825-288A>T intron_variant Intron 5 of 5 XP_047283475.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UCP3ENST00000314032.9 linkc.825-288A>T intron_variant Intron 6 of 6 1 NM_003356.4 ENSP00000323740.4 P55916-1
UCP3ENST00000545271.1 linkn.441A>T non_coding_transcript_exon_variant Exon 1 of 2 4
ENSG00000298570ENST00000756620.1 linkn.46+1399T>A intron_variant Intron 1 of 4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
235474
Hom.:
0
Cov.:
2
AF XY:
0.00
AC XY:
0
AN XY:
126838
African (AFR)
AF:
0.00
AC:
0
AN:
6766
American (AMR)
AF:
0.00
AC:
0
AN:
9696
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
6726
East Asian (EAS)
AF:
0.00
AC:
0
AN:
11850
South Asian (SAS)
AF:
0.00
AC:
0
AN:
35672
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10960
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
928
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
140188
Other (OTH)
AF:
0.00
AC:
0
AN:
12688
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
4.1
DANN
Benign
0.60
PhyloP100
-0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1685356; hg19: chr11-73712859; API