11-74001814-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003356.4(UCP3):c.825-288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 386,650 control chromosomes in the GnomAD database, including 72,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (34109 hom., cov: 31)
  • Exomes 𝑓: 0.56 (38070 hom.)
• Consequence: UCP3 NM_003356.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.468

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-74001814-T-C is Benign according to our data. Variant chr11-74001814-T-C is described in ClinVar as [Benign]. Clinvar id is 1254088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UCP3	NM_003356.4	c.825-288A>G		intron_variant		ENST00000314032.9
UCP3	XM_047427519.1	c.825-288A>G		intron_variant
UCP3	XR_007062495.1	n.3040A>G		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UCP3	ENST00000314032.9	c.825-288A>G		intron_variant		1	NM_003356.4	P1
UCP3	ENST00000545271.1	n.441A>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98877 AN: 151902 Hom.: 34058 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.614

GnomAD4 exome AF: 0.562 AC: 131830 AN: 234630 Hom.: 38070 Cov.: 2 AF XY: 0.563 AC XY: 71168 AN XY: 126406

Gnomad4 AFR exome AF: 0.908

Gnomad4 AMR exome AF: 0.541

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.612

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.530

Gnomad4 OTH exome AF: 0.569

GnomAD4 genome AF: 0.651 AC: 98987 AN: 152020 Hom.: 34109 Cov.: 31 AF XY: 0.652 AC XY: 48418 AN XY: 74292

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.611

Alfa AF: 0.583 Hom.: 6308

Bravo AF: 0.655

Asia WGS AF: 0.631 AC: 2192 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.2
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1685356; hg19: chr11-73712859;