11-74001725-GA-GAAAA

Variant names:

• chr11-74001725-G-GAAA
• rs11412246
• NM_003356.4:c.825-202_825-200dupTTT

Variant summary

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

The NM_003356.4(UCP3):​c.825-202_825-200dupTTT 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000025 (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.825-202_825-200dupTTT		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_825-199insTTT		intron	N/A	ENSP00000323740.4	P55916-1
	UCP3	ENST00000963037.1		c.783-200_783-199insTTT		intron	N/A	ENSP00000633096.1
	UCP3	ENST00000545271.1	TSL:4	n.515+14_515+15insTTT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000246 AC: 1 AN: 405706 Hom.: 0 Cov.: 4 AF XY: 0.00000465 AC XY: 1 AN XY: 215044

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

African (AFR) AF: 0.00 AC: 0 AN: 10890

American (AMR) AF: 0.00 AC: 0 AN: 16758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12140

East Asian (EAS) AF: 0.00 AC: 0 AN: 27534

South Asian (SAS) AF: 0.00 AC: 0 AN: 42798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1716

European-Non Finnish (NFE) AF: 0.00000408 AC: 1 AN: 245282

Other (OTH) AF: 0.00 AC: 0 AN: 23106

⚠️ 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 Cov.: 0

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;