rs11235971

Variant names:

• chr11-74002515-T-C
• rs11235971
• NM_003356.4:c.825-989A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-74002515-T-C
• chr11-74002515-T-G

Variant summary

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

The NM_003356.4(UCP3):​c.825-989A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,140 control chromosomes in the GnomAD database, including 3,966 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 0.22 (3966 hom., cov: 32)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCP3	NM_003356.4	c.825-989A>G		intron_variant	Intron 6 of 6	ENST00000314032.9	NP_003347.1
UCP3	XR_007062495.1	n.2339A>G		non_coding_transcript_exon_variant	Exon 6 of 7
UCP3	XM_047427519.1	c.825-989A>G		intron_variant	Intron 5 of 5		XP_047283475.1
UCP3	NM_022803.3	c.*1308A>G		downstream_gene_variant			NP_073714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.825-989A>G		intron_variant	Intron 6 of 6	1	NM_003356.4	ENSP00000323740.4
ENSG00000298570	ENST00000756620.1	n.47-1231T>C		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33165 AN: 152022 Hom.: 3970 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33167 AN: 152140 Hom.: 3966 Cov.: 32 AF XY: 0.224 AC XY: 16631 AN XY: 74376

African (AFR) AF: 0.157 AC: 6509 AN: 41522

American (AMR) AF: 0.149 AC: 2275 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3466

East Asian (EAS) AF: 0.291 AC: 1506 AN: 5170

South Asian (SAS) AF: 0.243 AC: 1175 AN: 4826

European-Finnish (FIN) AF: 0.381 AC: 4015 AN: 10548

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16398 AN: 68000

Other (OTH) AF: 0.182 AC: 385 AN: 2114

Alfa AF: 0.227 Hom.: 15138

Bravo AF: 0.194

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.80
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: rs11235971; hg19: chr11-73713560;