11-73978059-G-A

Position:

chr11-73978059-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003355.3(UCP2):c.164C>T(p.Ala55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,613,752 control chromosomes in the GnomAD database, including 137,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.43 ( 13830 hom., cov: 32)

Exomes 𝑓: 0.41 ( 123265 hom. )

Consequence

UCP2
NM_003355.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.01

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]

UCP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013258755).

BP6

Variant 11-73978059-G-A is Benign according to our data. Variant chr11-73978059-G-A is described in ClinVar as [Benign]. Clinvar id is 130697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP2	NM_003355.3 linkuse as main transcript	c.164C>T	p.Ala55Val	missense_variant	4/8	ENST00000663595.2	NP_003346.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
UCP2	ENST00000663595.2 linkuse as main transcript	c.164C>T	p.Ala55Val	missense_variant	4/8		NM_003355.3	ENSP00000499695	P1
UCP2	ENST00000310473.9 linkuse as main transcript	c.164C>T	p.Ala55Val	missense_variant	5/9	1		ENSP00000312029	P1
UCP2	ENST00000536983.5 linkuse as main transcript	c.164C>T	p.Ala55Val	missense_variant	4/7	5		ENSP00000441147
UCP2	ENST00000544615.5 linkuse as main transcript	n.83C>T		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64775

AN:

151882

Hom.:

13832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.406

GnomAD3 exomes

AF:

0.412

AC:

103341

AN:

250864

Hom.:

21712

AF XY:

0.404

AC XY:

54795

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.398

Gnomad SAS exome

AF:

0.343

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.407

GnomAD4 exome

AF:

0.409

AC:

597590

AN:

1461752

Hom.:

123265

Cov.:

AF XY:

0.406

AC XY:

295093

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.464

Gnomad4 ASJ exome

AF:

0.336

Gnomad4 EAS exome

AF:

0.446

Gnomad4 SAS exome

AF:

0.340

Gnomad4 FIN exome

AF:

0.460

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.426

AC:

64790

AN:

152000

Hom.:

13830

Cov.:

AF XY:

0.427

AC XY:

31714

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.454

Gnomad4 AMR

AF:

0.450

Gnomad4 ASJ

AF:

0.325

Gnomad4 EAS

AF:

0.426

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.467

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.405

Hom.:

28778

Bravo

AF:

0.428

TwinsUK

AF:

0.420

AC:

1558

ALSPAC

AF:

0.424

AC:

1633

ESP6500AA

AF:

0.437

AC:

1923

ESP6500EA

AF:

0.408

AC:

3503

ExAC

AF:

0.411

AC:

49899

Asia WGS

AF:

0.386

AC:

1342

AN:

3478

EpiCase

AF:

0.397

EpiControl

AF:

0.389

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 23132673, 10557023, 19950601, 19368944, 10071761, 19653005, 25158045, 18956255, 21751002, 23537071, 19895332) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.87

D;D;.

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.

MutationTaster

Benign

0.99

P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.91

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.12

MPC

0.057

ClinPred

0.011

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over