11-74001663-G-GTC

Position:

• chr11-74001663-G-GTC

Variant summary

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

The NM_003356.4(UCP3):​c.825-138_825-137insGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 711,692 control chromosomes in the GnomAD database, including 7,691 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2494 hom., cov: 28)
  • Exomes 𝑓: 0.15 (5197 hom.)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.517

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 11-74001663-G-GTC is Benign according to our data. Variant chr11-74001663-G-GTC is described in ClinVar as [Benign]. Clinvar id is 1286622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCP3	NM_003356.4	c.825-138_825-137insGA		intron_variant		ENST00000314032.9
UCP3	XM_047427519.1	c.825-138_825-137insGA		intron_variant
UCP3	XR_007062495.1	n.3114+76_3114+77insGA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCP3	ENST00000314032.9	c.825-138_825-137insGA		intron_variant		1	NM_003356.4	P1
UCP3	ENST00000545271.1	n.515+76_515+77insGA		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25072 AN: 148208 Hom.: 2492 Cov.: 28

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.153 AC: 85957 AN: 563386 Hom.: 5197 Cov.: 7 AF XY: 0.149 AC XY: 44601 AN XY: 298658

Gnomad4 AFR exome AF: 0.0592

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.0957

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.169 AC: 25076 AN: 148306 Hom.: 2494 Cov.: 28 AF XY: 0.166 AC XY: 12006 AN XY: 72314

Gnomad4 AFR AF: 0.0796

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.172

Asia WGS AF: 0.101 AC: 352 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 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3837411; hg19: chr11-73712708;