chr11-74002397-T-C

Variant names:

• chr11-74002397-T-C
• rs1726745
• NM_003356.4:c.825-871A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ENSG00000298570 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003356.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCP3	NM_003356.4	MANE Select	c.825-871A>G		intron	N/A	NP_003347.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCP3	ENST00000314032.9	TSL:1 MANE Select	c.825-871A>G		intron	N/A	ENSP00000323740.4
	ENSG00000298570	ENST00000756620.1		n.47-1349T>C		intron	N/A
	UCP3	ENST00000545271.1	TSL:4	n.-143A>G		upstream_gene	N/A

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

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AF: 0.278 AC: 5 AN: 18

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 8 AN: 14

East Asian (EAS) AF: 0.457 AC: 21 AN: 46

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.714 AC: 100 AN: 140

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.468 AC: 130 AN: 278

Other (OTH) AF: 0.433 AC: 13 AN: 30

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

African (AFR) AF: 0.661 AC: 27389 AN: 41432

American (AMR) AF: 0.530 AC: 8091 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1847 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2267 AN: 5170

South Asian (SAS) AF: 0.505 AC: 2426 AN: 4802

European-Finnish (FIN) AF: 0.598 AC: 6307 AN: 10548

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35395 AN: 67984

Other (OTH) AF: 0.529 AC: 1116 AN: 2110

Alfa AF: 0.528 Hom.: 16026

Bravo AF: 0.559

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.53
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1726745; hg19: chr11-73713442;