rs371789455

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003355.3(UCP2):c.446G>A(p.Arg149Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,613,892 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

UCP2
NM_003355.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.11

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

hyperinsulinism due to UCP2 deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

UCP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050816536).

BP6

Variant 11-73976909-C-T is Benign according to our data. Variant chr11-73976909-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 212541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 26 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003355.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UCP2	NM_003355.3	MANE Select	c.446G>A	p.Arg149Gln	missense	Exon 5 of 8	NP_003346.2
UCP2	NM_001381943.1		c.446G>A	p.Arg149Gln	missense	Exon 6 of 9	NP_001368872.1	P55851
UCP2	NM_001381944.1		c.446G>A	p.Arg149Gln	missense	Exon 5 of 8	NP_001368873.1	P55851

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UCP2	ENST00000663595.2	MANE Select	c.446G>A	p.Arg149Gln	missense	Exon 5 of 8	ENSP00000499695.1	P55851
UCP2	ENST00000310473.11	TSL:1	c.446G>A	p.Arg149Gln	missense	Exon 6 of 9	ENSP00000312029.3
UCP2	ENST00000880151.1		c.446G>A	p.Arg149Gln	missense	Exon 5 of 8	ENSP00000550210.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000620

AC:

156

AN:

251420

AF XY:

0.000515

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000131

AC:

192

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33478

American (AMR)

AF:

0.00391

AC:

175

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111848

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000171

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41450

American (AMR)

AF:

0.00137

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000124

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000626

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.099

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.85

M_CAP

Benign

0.027

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.35

PhyloP100

1.1

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.74

REVEL

Benign

0.18

Sift

Benign

0.21

Sift4G

Benign

0.21

Polyphen

0.015

Vest4

0.22

MVP

0.75

MPC

0.064

ClinPred

0.021

GERP RS

5.0

PromoterAI

0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.068

gMVP

0.59

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over