Genetic Variant NM_003356.4:c.825-871A>G (chr11-74002397-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003356.4(UCP3):c.825-871A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,536 control chromosomes in the GnomAD database, including 24,304 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 24223 hom., cov: 32)

Exomes 𝑓: 0.53 ( 81 hom. )

Consequence

UCP3
NM_003356.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

11 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UCP3	NM_003356.4 link	c.825-871A>G	intron_variant	Intron 6 of 6	ENST00000314032.9	NP_003347.1
UCP3	XR_007062495.1 link	n.2457A>G	non_coding_transcript_exon_variant	Exon 6 of 7
UCP3	XM_047427519.1 link	c.825-871A>G	intron_variant	Intron 5 of 5		XP_047283475.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
UCP3	ENST00000314032.9 link	c.825-871A>G	intron_variant	Intron 6 of 6	1	NM_003356.4	ENSP00000323740.4
ENSG00000298570	ENST00000756620.1 link	n.47-1349T>C	intron_variant	Intron 1 of 4
UCP3	ENST00000545271.1 link	n.-143A>G	upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85326

AN:

151884

Hom.:

24213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.661

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.598

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.534

GnomAD4 exome

AF:

0.528

AC:

282

AN:

534

Hom.:

AF XY:

0.529

AC XY:

164

AN XY:

310

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.278

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

AN:

East Asian (EAS)

AF:

0.457

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.714

AC:

100

AN:

140

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.468

AC:

130

AN:

278

Other (OTH)

AF:

0.433

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.562

AC:

85383

AN:

152002

Hom.:

24223

Cov.:

AF XY:

0.563

AC XY:

41820

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.661

AC:

27389

AN:

41432

American (AMR)

AF:

0.530

AC:

8091

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

1847

AN:

3472

East Asian (EAS)

AF:

0.438

AC:

2267

AN:

5170

South Asian (SAS)

AF:

0.505

AC:

2426

AN:

4802

European-Finnish (FIN)

AF:

0.598

AC:

6307

AN:

10548

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.521

AC:

35395

AN:

67984

Other (OTH)

AF:

0.529

AC:

1116

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1911

3821

5732

7642

9553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.528

Hom.:

16026

Bravo

AF:

0.559

Asia WGS

AF:

0.458

AC:

1592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

(source)

DANN

Benign

0.53

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over