11-74006202-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003356.4(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
NM_003356.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:5

Conservation

PhyloP100: 5.62

Publications

29 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]

UCP3 links:

ENSG00000298570 (HGNC:):

ENSG00000298570 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
UCP3	NM_003356.4 link	c.304G>A	p.Val102Ile	missense_variant	Exon 3 of 7	ENST00000314032.9	NP_003347.1	P55916-1A0A0S2Z4G5
UCP3	NM_022803.3 link	c.304G>A	p.Val102Ile	missense_variant	Exon 3 of 6		NP_073714.1	P55916-2
UCP3	XM_047427519.1 link	c.304G>A	p.Val102Ile	missense_variant	Exon 2 of 6		XP_047283475.1
UCP3	XR_007062495.1 link	n.507G>A		non_coding_transcript_exon_variant	Exon 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UCP3	ENST00000314032.9 link	c.304G>A	p.Val102Ile	missense_variant	Exon 3 of 7	1	NM_003356.4	ENSP00000323740.4	P55916-1
UCP3	ENST00000426995.2 link	c.304G>A	p.Val102Ile	missense_variant	Exon 3 of 6	1		ENSP00000392143.2	P55916-2
ENSG00000298570	ENST00000756620.1 link	n.419+1185C>T		intron_variant	Intron 3 of 4
UCP3	ENST00000544614.1 link	c.*15G>A		downstream_gene_variant		4		ENSP00000445279.1	F5H3N5

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

GnomAD2 exomes

AF:

0.0102

AC:

2547

AN:

250432

AF XY:

0.00756

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 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

African (AFR)

AF:

0.132

AC:

4421

AN:

33480

American (AMR)

AF:

0.00789

AC:

353

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00119

AC:

103

AN:

86256

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.0224

AC:

129

AN:

5768

European-Non Finnish (NFE)

AF:

0.000997

AC:

1109

AN:

1112002

Other (OTH)

AF:

0.0103

AC:

620

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

413

825

1238

1650

2063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0371

AC:

5655

AN:

152272

Hom.:

339

Cov.:

AF XY:

0.0353

AC XY:

2629

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.127

AC:

5281

AN:

41532

American (AMR)

AF:

0.0131

AC:

200

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00131

AC:

AN:

68020

Other (OTH)

AF:

0.0284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

248

497

745

994

1242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00924

Hom.:

138

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Obesity, severe, and type II diabetes

Pathogenic:1

Oct 01, 1998

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Inherited obesity

Benign:1

Feb 06, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Short-rib thoracic dysplasia 13 with or without polydactyly

Benign:1

Dec 17, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

UCP3 POLYMORPHISM G/A

Benign:1

Oct 01, 1998

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

5.6

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

Mutation Taster

=89/11

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over