rs3741135

Positions:

• chr11-74002915-G-A

Variant summary

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

The ENST00000314032.9(UCP3):​c.824+912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 984,872 control chromosomes in the GnomAD database, including 28,842 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 0.24 (4572 hom., cov: 33)
  • Exomes 𝑓: 0.24 (24270 hom.)
• Consequence: UCP3 ENST00000314032.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP3	NM_003356.4	c.824+912C>T		intron_variant		ENST00000314032.9	NP_003347.1
UCP3	NM_022803.3	c.*908C>T		3_prime_UTR_variant	6/6		NP_073714.1
UCP3	XM_047427519.1	c.824+912C>T		intron_variant			XP_047283475.1
UCP3	XR_007062495.1	n.1939C>T		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.824+912C>T		intron_variant		1	NM_003356.4	ENSP00000323740	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36338 AN: 152036 Hom.: 4575 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.241 AC: 200700 AN: 832716 Hom.: 24270 Cov.: 30 AF XY: 0.241 AC XY: 92784 AN XY: 384566

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.239 AC: 36359 AN: 152156 Hom.: 4572 Cov.: 33 AF XY: 0.243 AC XY: 18105 AN XY: 74386

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.196

Alfa AF: 0.238 Hom.: 2485

Bravo AF: 0.218

Asia WGS AF: 0.250 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3741135; hg19: chr11-73713960;