11-74001725-GA-GAA

Variant names:

• chr11-74001725-G-GA
• rs11412246
• NM_003356.4:c.825-200dupT

Variant summary

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

The NM_003356.4(UCP3):​c.825-200dupT 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
• 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 11-74001725-G-GA is Benign according to our data. Variant chr11-74001725-G-GA is described in ClinVar as Benign. ClinVar VariationId 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.

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

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

African (AFR) AF: 0.385 AC: 4176 AN: 10836

American (AMR) AF: 0.339 AC: 5631 AN: 16624

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 3379 AN: 12042

East Asian (EAS) AF: 0.166 AC: 4533 AN: 27334

South Asian (SAS) AF: 0.261 AC: 11101 AN: 42496

European-Finnish (FIN) AF: 0.199 AC: 5049 AN: 25314

Middle Eastern (MID) AF: 0.333 AC: 571 AN: 1714

European-Non Finnish (NFE) AF: 0.251 AC: 61180 AN: 243510

Other (OTH) AF: 0.269 AC: 6168 AN: 22910

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

African (AFR) AF: 0.426 AC: 17232 AN: 40448

American (AMR) AF: 0.370 AC: 5573 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1095 AN: 3448

East Asian (EAS) AF: 0.145 AC: 742 AN: 5102

South Asian (SAS) AF: 0.261 AC: 1231 AN: 4714

European-Finnish (FIN) AF: 0.209 AC: 2077 AN: 9920

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18849 AN: 67510

Other (OTH) AF: 0.332 AC: 689 AN: 2076

Alfa AF: 0.103 Hom.: 147

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		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11412246; hg19: chr11-73712770; COSMIC: COSV107382647; COSMIC: COSV107382647;