chr11-74006202-C-T

Position:

chr11-74006202-C-T

Variant summary

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

The ENST00000314032.9(UCP3):c.304G>A(p.Val102Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00769 in 1,614,100 control chromosomes in the GnomAD database, including 676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 339 hom., cov: 33)

Exomes 𝑓: 0.0046 ( 337 hom. )

Consequence

UCP3
ENST00000314032.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 5.62

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]

UCP3 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=0.0023040771).

BP6

Variant 11-74006202-C-T is Benign according to our data. Variant chr11-74006202-C-T is described in ClinVar as [Benign]. Clinvar id is 7576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UCP3	NM_003356.4 linkuse as main transcript	c.304G>A	p.Val102Ile	missense_variant	3/7	ENST00000314032.9	NP_003347.1
UCP3	NM_022803.3 linkuse as main transcript	c.304G>A	p.Val102Ile	missense_variant	3/6		NP_073714.1
UCP3	XM_047427519.1 linkuse as main transcript	c.304G>A	p.Val102Ile	missense_variant	2/6		XP_047283475.1
UCP3	XR_007062495.1 linkuse as main transcript	n.507G>A		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9 linkuse as main transcript	c.304G>A	p.Val102Ile	missense_variant	3/7	1	NM_003356.4	ENSP00000323740	P1	P55916-1
UCP3	ENST00000426995.2 linkuse as main transcript	c.304G>A	p.Val102Ile	missense_variant	3/6	1		ENSP00000392143		P55916-2
UCP3	ENST00000544614.1 linkuse as main transcript			downstream_gene_variant		4		ENSP00000445279

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5638

AN:

152154

Hom.:

336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0102

AC:

2547

AN:

250432

Hom.:

133

AF XY:

0.00756

AC XY:

1024

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.00709

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00784

GnomAD4 exome

AF:

0.00462

AC:

6758

AN:

1461828

Hom.:

337

Cov.:

AF XY:

0.00400

AC XY:

2912

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.00789

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000997

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.0371

AC:

5655

AN:

152272

Hom.:

339

Cov.:

AF XY:

0.0353

AC XY:

2629

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.00725

Hom.:

Bravo

AF:

0.0411

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.119

AC:

524

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.0126

AC:

1528

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00166

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Obesity, severe, and type II diabetes

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 1998

- -

Short-rib thoracic dysplasia 13 with or without polydactyly

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 17, 2024

- -

UCP3 POLYMORPHISM G/A

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Oct 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

0.015

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.0015

P;P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.79

N;N

REVEL

Uncertain

0.45

Sift

Benign

0.044

D;D

Sift4G

Benign

0.14

T;T

Polyphen

0.045

B;.

Vest4

0.14

MPC

0.037

ClinPred

0.013

GERP RS

5.8

Varity_R

0.29

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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