rs1685354

Variant names:

• chr11-74002546-A-G
• rs1685354
• NM_003356.4:c.825-1020T>C

Variant summary

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

The NM_003356.4(UCP3):​c.825-1020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,090 control chromosomes in the GnomAD database, including 7,385 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 0.30 (7385 hom., cov: 32)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 22 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 (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCP3	NM_003356.4	c.825-1020T>C		intron_variant	Intron 6 of 6	ENST00000314032.9	NP_003347.1
UCP3	XR_007062495.1	n.2308T>C		non_coding_transcript_exon_variant	Exon 6 of 7
UCP3	XM_047427519.1	c.825-1020T>C		intron_variant	Intron 5 of 5		XP_047283475.1
UCP3	NM_022803.3	c.*1277T>C		downstream_gene_variant			NP_073714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.825-1020T>C		intron_variant	Intron 6 of 6	1	NM_003356.4	ENSP00000323740.4
ENSG00000298570	ENST00000756620.1	n.47-1200A>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45529 AN: 151972 Hom.: 7383 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.300 AC: 45562 AN: 152090 Hom.: 7385 Cov.: 32 AF XY: 0.296 AC XY: 22033 AN XY: 74326

African (AFR) AF: 0.423 AC: 17513 AN: 41450

American (AMR) AF: 0.338 AC: 5163 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3468

East Asian (EAS) AF: 0.147 AC: 761 AN: 5176

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4820

European-Finnish (FIN) AF: 0.211 AC: 2238 AN: 10600

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17020 AN: 67992

Other (OTH) AF: 0.283 AC: 595 AN: 2106

Alfa AF: 0.272 Hom.: 16618

Bravo AF: 0.316

Asia WGS AF: 0.191 AC: 664 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	3.3
DANN	Benign	0.59
PhyloP100		-0.36
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: rs1685354; hg19: chr11-73713591;