rs647126

Variant names:

• chr11-74000975-A-G
• rs647126
• NM_003356.4:c.*437T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003356.4(UCP3):​c.*437T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 204,644 control chromosomes in the GnomAD database, including 34,883 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 0.60 (28043 hom., cov: 31)
  • Exomes 𝑓: 0.50 (6840 hom.)
• Consequence: UCP3 NM_003356.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 28 publications found

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]

ENSG00000298570 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCP3	NM_003356.4	c.*437T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000314032.9	NP_003347.1
UCP3	XR_007062495.1	n.3666T>C		non_coding_transcript_exon_variant	Exon 7 of 7
UCP3	XM_047427519.1	c.*437T>C		3_prime_UTR_variant	Exon 6 of 6		XP_047283475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.*437T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_003356.4	ENSP00000323740.4
ENSG00000298570	ENST00000756620.1	n.46+560A>G		intron_variant	Intron 1 of 4
ENSG00000298594	ENST00000756716.1	n.493-232A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90639 AN: 151848 Hom.: 28012 Cov.: 31

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.495 AC: 26078 AN: 52678 Hom.: 6840 Cov.: 0 AF XY: 0.489 AC XY: 13615 AN XY: 27834

African (AFR) AF: 0.766 AC: 840 AN: 1096

American (AMR) AF: 0.520 AC: 1684 AN: 3238

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 686 AN: 1422

East Asian (EAS) AF: 0.457 AC: 1576 AN: 3446

South Asian (SAS) AF: 0.482 AC: 1914 AN: 3970

European-Finnish (FIN) AF: 0.554 AC: 1904 AN: 3434

Middle Eastern (MID) AF: 0.540 AC: 122 AN: 226

European-Non Finnish (NFE) AF: 0.483 AC: 15866 AN: 32852

Other (OTH) AF: 0.496 AC: 1486 AN: 2994

GnomAD4 genome AF: 0.597 AC: 90724 AN: 151966 Hom.: 28043 Cov.: 31 AF XY: 0.597 AC XY: 44317 AN XY: 74270

African (AFR) AF: 0.782 AC: 32409 AN: 41464

American (AMR) AF: 0.545 AC: 8323 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1844 AN: 3466

East Asian (EAS) AF: 0.438 AC: 2257 AN: 5156

South Asian (SAS) AF: 0.506 AC: 2431 AN: 4800

European-Finnish (FIN) AF: 0.598 AC: 6305 AN: 10538

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35415 AN: 67954

Other (OTH) AF: 0.563 AC: 1191 AN: 2114

Alfa AF: 0.559 Hom.: 13045

Bravo AF: 0.600

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.33
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs647126; hg19: chr11-73712020;