rs15763

chr11-74000432-A-Gchr11-74000432-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003356.4(UCP3):c.*980T>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 0.704 in 145,490 control chromosomes in the GnomAD database, including 36,405 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 0.70 (36270 hom., cov: 20)
  • Exomes 𝑓: 0.79 (135 hom.)
• Consequence: UCP3 NM_003356.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCP3	NM_003356.4	c.*980T>C		3_prime_UTR_variant	7/7	ENST00000314032.9
UCP3	XM_047427519.1	c.*980T>C		3_prime_UTR_variant	6/6
UCP3	XR_007062495.1	n.4209T>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCP3	ENST00000314032.9	c.*980T>C		3_prime_UTR_variant	7/7	1	NM_003356.4	P1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 101947 AN: 144942 Hom.: 36241 Cov.: 20

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.716

GnomAD4 exome AF: 0.794 AC: 340 AN: 428 Hom.: 135 Cov.: 0 AF XY: 0.814 AC XY: 210 AN XY: 258

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.798

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.703 AC: 102031 AN: 145062 Hom.: 36270 Cov.: 20 AF XY: 0.706 AC XY: 49599 AN XY: 70284

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.789

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.720

Alfa AF: 0.733 Hom.: 21136

Bravo AF: 0.687

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.27

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: rs15763; hg19: chr11-73711477;