rs647126

Positions:

• chr11-74000975-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
UCP3	NM_003356.4	c.*437T>C		3_prime_UTR_variant	7/7	ENST00000314032.9	NP_003347.1
UCP3	XM_047427519.1	c.*437T>C		3_prime_UTR_variant	6/6		XP_047283475.1
UCP3	XR_007062495.1	n.3666T>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.*437T>C		3_prime_UTR_variant	7/7	1	NM_003356.4	ENSP00000323740	P1

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

Gnomad4 AFR exome AF: 0.766

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.496

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

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.563

Alfa AF: 0.558 Hom.: 7902

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

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

LitVar

Other links and lift over

dbSNP: rs647126; hg19: chr11-73712020;