NM_003355.3:c.853G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003355.3(UCP2):ā€‹c.853G>Cā€‹(p.Val285Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,578 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

UCP2
NM_003355.3 missense

Scores

4
7
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37
Variant links:
Genes affected
UCP2 (HGNC:12518): (uncoupling protein 2) 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. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. This gene is expressed in many tissues, with the greatest expression in skeletal muscle. It is thought to play a role in nonshivering thermogenesis, obesity and diabetes. Chromosomal order is 5'-UCP3-UCP2-3'. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UCP2NM_003355.3 linkc.853G>C p.Val285Leu missense_variant Exon 8 of 8 ENST00000663595.2 NP_003346.2 P55851A0A024R5N5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UCP2ENST00000663595.2 linkc.853G>C p.Val285Leu missense_variant Exon 8 of 8 NM_003355.3 ENSP00000499695.1 P55851
UCP2ENST00000310473.9 linkc.853G>C p.Val285Leu missense_variant Exon 9 of 9 1 ENSP00000312029.3 P55851
UCP2ENST00000536983.5 linkc.672G>C p.Thr224Thr synonymous_variant Exon 7 of 7 5 ENSP00000441147.1 F5GX45
UCP2ENST00000544615.5 linkn.772G>C non_coding_transcript_exon_variant Exon 5 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152000
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461578
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152000
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74240
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D;.
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.54
D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
1.4
L;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.8
N;N
REVEL
Uncertain
0.49
Sift
Uncertain
0.0030
D;D
Sift4G
Benign
0.26
T;T
Polyphen
0.018
B;.
Vest4
0.65
MutPred
0.72
Loss of MoRF binding (P = 0.1002);.;
MVP
0.72
MPC
0.064
ClinPred
0.81
D
GERP RS
6.0
Varity_R
0.44
gMVP
0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs546507804; hg19: chr11-73686129; API