rs11235971

Positions:

• chr11-74002515-T-C
• chr11-74002515-T-G

Variant summary

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

The NM_003356.4(UCP3):​c.825-989A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,140 control chromosomes in the GnomAD database, including 3,966 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 0.22 (3966 hom., cov: 32)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCP3	NM_003356.4	c.825-989A>G		intron_variant		ENST00000314032.9
UCP3	XM_047427519.1	c.825-989A>G		intron_variant
UCP3	XR_007062495.1	n.2339A>G		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCP3	ENST00000314032.9	c.825-989A>G		intron_variant		1	NM_003356.4	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33165 AN: 152022 Hom.: 3970 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33167 AN: 152140 Hom.: 3966 Cov.: 32 AF XY: 0.224 AC XY: 16631 AN XY: 74376

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.182

Alfa AF: 0.224 Hom.: 6362

Bravo AF: 0.194

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.66

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: rs11235971; hg19: chr11-73713560;