11-74001725-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003356.4(UCP3):c.825-200_825-199insT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8117 hom., cov: 0)
  • Exomes 𝑓: 0.25 (10418 hom.)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24

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 -10 ACMG points.

• BP6: Variant 11-74001725-G-GA is Benign according to our data. Variant chr11-74001725-G-GA is described in ClinVar as [Benign]. Clinvar id is 1179763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCP3	NM_003356.4	c.825-200_825-199insT		intron_variant		ENST00000314032.9
UCP3	XM_047427519.1	c.825-200_825-199insT		intron_variant
UCP3	XR_007062495.1	n.3114+14_3114+15insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCP3	ENST00000314032.9	c.825-200_825-199insT		intron_variant		1	NM_003356.4	P1
UCP3	ENST00000545271.1	n.515+14_515+15insT		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.320 AC: 47842 AN: 149384 Hom.: 8119 Cov.: 0

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.253 AC: 101788 AN: 402780 Hom.: 10418 Cov.: 4 AF XY: 0.252 AC XY: 53827 AN XY: 213526

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.320 AC: 47865 AN: 149478 Hom.: 8117 Cov.: 0 AF XY: 0.316 AC XY: 23007 AN XY: 72734

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.332

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11412246; hg19: chr11-73712770;