rs2632723

chr11-74002084-T-C

Variant summary

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

The NM_003356.4(UCP3):c.825-558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 156,686 control chromosomes in the GnomAD database, including 2,995 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 0.19 (2930 hom., cov: 32)
  • Exomes 𝑓: 0.16 (65 hom.)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCP3	NM_003356.4	c.825-558A>G		intron_variant		ENST00000314032.9
UCP3	XM_047427519.1	c.825-558A>G		intron_variant
UCP3	XR_007062495.1	n.2770A>G		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCP3	ENST00000314032.9	c.825-558A>G		intron_variant		1	NM_003356.4	P1
UCP3	ENST00000545271.1	n.171A>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28835 AN: 152092 Hom.: 2926 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.159 AC: 711 AN: 4476 Hom.: 65 Cov.: 0 AF XY: 0.160 AC XY: 403 AN XY: 2514

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.0922

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.190 AC: 28855 AN: 152210 Hom.: 2930 Cov.: 32 AF XY: 0.186 AC XY: 13827 AN XY: 74428

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.187

Alfa AF: 0.198 Hom.: 624

Bravo AF: 0.198

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.0
Dann	Benign	0.73

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: rs2632723; hg19: chr11-73713129;