rs11235972

Variant names:

• chr11-74006029-G-A
• rs11235972
• NM_003356.4:c.338-96C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003356.4(UCP3):​c.338-96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,560,654 control chromosomes in the GnomAD database, including 45,438 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3774 hom., cov: 32)
  • Exomes 𝑓: 0.24 (41664 hom.)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 25 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 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.338-96C>T		intron	N/A	NP_003347.1
	UCP3	NM_022803.3		c.338-96C>T		intron	N/A	NP_073714.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCP3	ENST00000314032.9	TSL:1 MANE Select	c.338-96C>T		intron	N/A	ENSP00000323740.4
	UCP3	ENST00000426995.2	TSL:1	c.338-96C>T		intron	N/A	ENSP00000392143.2
	UCP3	ENST00000963037.1		c.338-138C>T		intron	N/A	ENSP00000633096.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32246 AN: 151992 Hom.: 3776 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.239 AC: 336050 AN: 1408542 Hom.: 41664 Cov.: 30 AF XY: 0.239 AC XY: 166829 AN XY: 697320

African (AFR) AF: 0.123 AC: 3987 AN: 32364

American (AMR) AF: 0.131 AC: 4891 AN: 37278

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 5896 AN: 25186

East Asian (EAS) AF: 0.285 AC: 10716 AN: 37618

South Asian (SAS) AF: 0.233 AC: 19036 AN: 81566

European-Finnish (FIN) AF: 0.364 AC: 18191 AN: 50008

Middle Eastern (MID) AF: 0.106 AC: 595 AN: 5594

European-Non Finnish (NFE) AF: 0.240 AC: 259451 AN: 1080508

Other (OTH) AF: 0.227 AC: 13287 AN: 58420

GnomAD4 genome AF: 0.212 AC: 32246 AN: 152112 Hom.: 3774 Cov.: 32 AF XY: 0.217 AC XY: 16147 AN XY: 74354

African (AFR) AF: 0.132 AC: 5462 AN: 41528

American (AMR) AF: 0.151 AC: 2302 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1571 AN: 5172

South Asian (SAS) AF: 0.234 AC: 1128 AN: 4824

European-Finnish (FIN) AF: 0.379 AC: 4001 AN: 10558

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16472 AN: 67964

Other (OTH) AF: 0.175 AC: 369 AN: 2110

Alfa AF: 0.213 Hom.: 787

Bravo AF: 0.189

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.32
DANN	Benign	0.57
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11235972; hg19: chr11-73717074; COSMIC: COSV58368542; COSMIC: COSV58368542;