rs2734827

Positions:

• chr11-74005232-G-A
• chr11-74005232-G-C

Variant summary

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

The ENST00000314032.9(UCP3):​c.541+498C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,004 control chromosomes in the GnomAD database, including 12,389 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 0.39 (12389 hom., cov: 32)
• Consequence: UCP3 ENST00000314032.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP3	NM_003356.4	c.541+498C>T		intron_variant		ENST00000314032.9	NP_003347.1
UCP3	NM_022803.3	c.541+498C>T		intron_variant			NP_073714.1
UCP3	XM_047427519.1	c.541+498C>T		intron_variant			XP_047283475.1
UCP3	XR_007062495.1	n.744+498C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.541+498C>T		intron_variant		1	NM_003356.4	ENSP00000323740	P1
UCP3	ENST00000426995.2	c.541+498C>T		intron_variant		1		ENSP00000392143

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59582 AN: 151888 Hom.: 12377 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.392 AC: 59644 AN: 152004 Hom.: 12389 Cov.: 32 AF XY: 0.386 AC XY: 28701 AN XY: 74314

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.384

Alfa AF: 0.359 Hom.: 5978

Bravo AF: 0.409

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.67

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: rs2734827; hg19: chr11-73716277;