rs753260142

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003355.3(UCP2):​c.800G>T​(p.Arg267Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

UCP2
NM_003355.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.262
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.063155174).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UCP2NM_003355.3 linkc.800G>T p.Arg267Leu missense_variant Exon 7 of 8 ENST00000663595.2 NP_003346.2 P55851A0A024R5N5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UCP2ENST00000663595.2 linkc.800G>T p.Arg267Leu missense_variant Exon 7 of 8 NM_003355.3 ENSP00000499695.1 P55851

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250382
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135224
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458574
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
725168
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
17
DANN
Benign
0.89
DEOGEN2
Benign
0.12
T;.
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.84
T;.
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.063
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.10
N;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
0.10
N;N
REVEL
Benign
0.22
Sift
Benign
0.94
T;T
Sift4G
Benign
0.96
T;T
Polyphen
0.0
B;.
Vest4
0.25
MutPred
0.45
Loss of methylation at R267 (P = 0.0099);.;
MVP
0.58
MPC
0.068
ClinPred
0.072
T
GERP RS
0.24
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.074
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs753260142; hg19: chr11-73686551; API