NM_003356.4:c.630C>T

Variant names:

• chr11-74004497-G-A
• rs2075577
• NM_003356.4:c.630C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003356.4(UCP3):​c.630C>T​(p.Tyr210Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,613,248 control chromosomes in the GnomAD database, including 254,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30748 hom., cov: 33)
  • Exomes 𝑓: 0.55 (223399 hom.)
• Consequence: UCP3 NM_003356.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.622
• Publications: 50 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-74004497-G-A is Benign according to our data. Variant chr11-74004497-G-A is described in ClinVar as Benign. ClinVar VariationId is 1221961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.622 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 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.630C>T	p.Tyr210Tyr	synonymous	Exon 5 of 7	NP_003347.1	P55916-1
	UCP3	NM_022803.3		c.630C>T	p.Tyr210Tyr	synonymous	Exon 5 of 6	NP_073714.1	P55916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCP3	ENST00000314032.9	TSL:1 MANE Select	c.630C>T	p.Tyr210Tyr	synonymous	Exon 5 of 7	ENSP00000323740.4	P55916-1
	UCP3	ENST00000426995.2	TSL:1	c.630C>T	p.Tyr210Tyr	synonymous	Exon 5 of 6	ENSP00000392143.2	P55916-2
	UCP3	ENST00000963037.1		c.588C>T	p.Tyr196Tyr	synonymous	Exon 5 of 7	ENSP00000633096.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94869 AN: 152026 Hom.: 30710 Cov.: 33

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.593

GnomAD2 exomes AF: 0.557 AC: 139881 AN: 251196 AF XY: 0.552

Gnomad AFR exome AF: 0.819

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.411

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.550

Gnomad OTH exome AF: 0.554

GnomAD4 exome AF: 0.549 AC: 802787 AN: 1461102 Hom.: 223399 Cov.: 44 AF XY: 0.548 AC XY: 398017 AN XY: 726868

African (AFR) AF: 0.823 AC: 27541 AN: 33464

American (AMR) AF: 0.531 AC: 23726 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 14168 AN: 26128

East Asian (EAS) AF: 0.475 AC: 18867 AN: 39682

South Asian (SAS) AF: 0.526 AC: 45367 AN: 86228

European-Finnish (FIN) AF: 0.625 AC: 33355 AN: 53400

Middle Eastern (MID) AF: 0.523 AC: 3010 AN: 5754

European-Non Finnish (NFE) AF: 0.543 AC: 603709 AN: 1111390

Other (OTH) AF: 0.547 AC: 33044 AN: 60366

GnomAD4 genome AF: 0.624 AC: 94960 AN: 152146 Hom.: 30748 Cov.: 33 AF XY: 0.623 AC XY: 46303 AN XY: 74378

African (AFR) AF: 0.815 AC: 33840 AN: 41528

American (AMR) AF: 0.556 AC: 8500 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1885 AN: 3470

East Asian (EAS) AF: 0.441 AC: 2276 AN: 5158

South Asian (SAS) AF: 0.511 AC: 2465 AN: 4822

European-Finnish (FIN) AF: 0.633 AC: 6695 AN: 10578

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37335 AN: 67984

Other (OTH) AF: 0.587 AC: 1234 AN: 2104

Alfa AF: 0.563 Hom.: 46489

Bravo AF: 0.625

Asia WGS AF: 0.478 AC: 1661 AN: 3478

EpiCase AF: 0.527

EpiControl AF: 0.523

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	UCP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.66
DANN	Benign	0.42
PhyloP100		-0.62
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: rs2075577; hg19: chr11-73715542; COSMIC: COSV58368214; COSMIC: COSV58368214;