11-74001663-G-GTC

Variant names:

• chr11-74001663-G-GTC
• rs3837411
• NM_003356.4:c.825-139_825-138dupGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003356.4(UCP3):​c.825-139_825-138dupGA 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
• Publications: 0 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCP3	NM_003356.4	MANE Select	c.825-139_825-138dupGA		intron	N/A	NP_003347.1	P55916-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCP3	ENST00000314032.9	TSL:1 MANE Select	c.825-138_825-137insGA		intron	N/A	ENSP00000323740.4	P55916-1
	UCP3	ENST00000963037.1		c.783-138_783-137insGA		intron	N/A	ENSP00000633096.1
	UCP3	ENST00000545271.1	TSL:4	n.515+76_515+77insGA		intron	N/A

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

African (AFR) AF: 0.0592 AC: 889 AN: 15012

American (AMR) AF: 0.214 AC: 5498 AN: 25684

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 1980 AN: 18086

East Asian (EAS) AF: 0.165 AC: 5137 AN: 31114

South Asian (SAS) AF: 0.0957 AC: 5343 AN: 55858

European-Finnish (FIN) AF: 0.153 AC: 6259 AN: 41020

Middle Eastern (MID) AF: 0.136 AC: 389 AN: 2862

European-Non Finnish (NFE) AF: 0.163 AC: 55878 AN: 343792

Other (OTH) AF: 0.153 AC: 4584 AN: 29958

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

African (AFR) AF: 0.0796 AC: 3089 AN: 38808

American (AMR) AF: 0.270 AC: 4066 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 449 AN: 3450

East Asian (EAS) AF: 0.136 AC: 700 AN: 5158

South Asian (SAS) AF: 0.105 AC: 493 AN: 4692

European-Finnish (FIN) AF: 0.166 AC: 1694 AN: 10232

Middle Eastern (MID) AF: 0.203 AC: 59 AN: 290

European-Non Finnish (NFE) AF: 0.207 AC: 14019 AN: 67658

Other (OTH) AF: 0.172 AC: 355 AN: 2060

Alfa AF: 0.0587 Hom.: 112

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3837411; hg19: chr11-73712708; COSMIC: COSV58369125; COSMIC: COSV58369125;