rs201948640

Variant names:

• chr11-74001489-C-A
• rs201948640
• NM_003356.4:c.862G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-74001489-C-A
• chr11-74001489-C-G
• chr11-74001489-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003356.4(UCP3):​c.862G>T​(p.Val288Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UCP3 NM_003356.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCP3	NM_003356.4	c.862G>T	p.Val288Leu	missense_variant	Exon 7 of 7	ENST00000314032.9	NP_003347.1
UCP3	XM_047427519.1	c.862G>T	p.Val288Leu	missense_variant	Exon 6 of 6		XP_047283475.1
UCP3	XR_007062495.1	n.3152G>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCP3	ENST00000314032.9	c.862G>T	p.Val288Leu	missense_variant	Exon 7 of 7	1	NM_003356.4	ENSP00000323740.4
UCP3	ENST00000545271.1	n.553G>T		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.29	T
Polyphen		0.16	B
Vest4		0.36
MutPred		0.78		Loss of MoRF binding (P = 0.1006);
MVP		0.55
MPC		0.061
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.48
gMVP		0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs201948640; hg19: chr11-73712534; COSMIC: COSV105191660; COSMIC: COSV105191660;