chr11-74001725-G-GAA

Variant names:

• chr11-74001725-G-GAA
• rs11412246
• NM_003356.4:c.825-201_825-200dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003356.4(UCP3):​c.825-201_825-200dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.825-201_825-200dupTT		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.825-200_825-199insTT		intron	N/A	ENSP00000323740.4	P55916-1
	UCP3	ENST00000963037.1		c.783-200_783-199insTT		intron	N/A	ENSP00000633096.1
	UCP3	ENST00000545271.1	TSL:4	n.515+14_515+15insTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000736 AC: 11 AN: 149542 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00350 AC: 1409 AN: 402368 Hom.: 0 Cov.: 4 AF XY: 0.00329 AC XY: 701 AN XY: 213234

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00748 AC: 80 AN: 10698

American (AMR) AF: 0.00559 AC: 92 AN: 16472

Ashkenazi Jewish (ASJ) AF: 0.00456 AC: 55 AN: 12056

East Asian (EAS) AF: 0.00211 AC: 58 AN: 27462

South Asian (SAS) AF: 0.00328 AC: 139 AN: 42378

European-Finnish (FIN) AF: 0.00189 AC: 48 AN: 25352

Middle Eastern (MID) AF: 0.00767 AC: 13 AN: 1694

European-Non Finnish (NFE) AF: 0.00347 AC: 844 AN: 243340

Other (OTH) AF: 0.00349 AC: 80 AN: 22916

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000735 AC: 11 AN: 149636 Hom.: 0 Cov.: 0 AF XY: 0.0000824 AC XY: 6 AN XY: 72826

African (AFR) AF: 0.000247 AC: 10 AN: 40510

American (AMR) AF: 0.00 AC: 0 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9938

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67552

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.000101 Hom.: 147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs11412246; hg19: chr11-73712770;