rs1726745

Positions:

• chr11-74002397-T-C
• chr11-74002397-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.825-871A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,536 control chromosomes in the GnomAD database, including 24,304 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 0.56 (24223 hom., cov: 32)
  • Exomes 𝑓: 0.53 (81 hom.)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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]

UCP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP3	NM_003356.4	c.825-871A>G		intron_variant		ENST00000314032.9	NP_003347.1
UCP3	XM_047427519.1	c.825-871A>G		intron_variant			XP_047283475.1
UCP3	XR_007062495.1	n.2457A>G		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.825-871A>G		intron_variant		1	NM_003356.4	ENSP00000323740.4

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85326 AN: 151884 Hom.: 24213 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.534

GnomAD4 exome AF: 0.528 AC: 282 AN: 534 Hom.: 81 AF XY: 0.529 AC XY: 164 AN XY: 310

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.433

GnomAD4 genome AF: 0.562 AC: 85383 AN: 152002 Hom.: 24223 Cov.: 32 AF XY: 0.563 AC XY: 41820 AN XY: 74292

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.529

Alfa AF: 0.533 Hom.: 8428

Bravo AF: 0.559

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.53

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: rs1726745; hg19: chr11-73713442;