rs1626521

Positions:

• chr11-74003294-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003356.4(UCP3):​c.824+533C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,112 control chromosomes in the GnomAD database, including 8,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8247 hom., cov: 32)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.249

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-74003294-G-A is Benign according to our data. Variant chr11-74003294-G-A is described in ClinVar as [Benign]. Clinvar id is 1277754.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP3	NM_003356.4	c.824+533C>T		intron_variant		ENST00000314032.9	NP_003347.1
UCP3	NM_022803.3	c.*529C>T		3_prime_UTR_variant	6/6		NP_073714.1
UCP3	XM_047427519.1	c.824+533C>T		intron_variant			XP_047283475.1
UCP3	XR_007062495.1	n.1560C>T		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.824+533C>T		intron_variant		1	NM_003356.4	ENSP00000323740	P1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48588 AN: 151994 Hom.: 8244 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.320 AC: 48624 AN: 152112 Hom.: 8247 Cov.: 32 AF XY: 0.316 AC XY: 23530 AN XY: 74358

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.331

Alfa AF: 0.292 Hom.: 2841

Bravo AF: 0.338

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 02, 2020

This variant is associated with the following publications: (PMID: 25755013) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.22

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: rs1626521; hg19: chr11-73714339;