chr11-74001814-T-C

Variant names:

• chr11-74001814-T-C
• rs1685356
• NM_003356.4:c.825-288A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.468
• Publications: 16 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 -20 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 VariationId is 1254088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 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.825-288A>G		intron	N/A	NP_003347.1	P55916-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UCP3	ENST00000314032.9	TSL:1 MANE Select	c.825-288A>G		intron	N/A	ENSP00000323740.4	P55916-1
	UCP3	ENST00000963037.1		c.783-288A>G		intron	N/A	ENSP00000633096.1
	UCP3	ENST00000545271.1	TSL:4	n.441A>G		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.908 AC: 6136 AN: 6756

American (AMR) AF: 0.541 AC: 5226 AN: 9662

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 3702 AN: 6694

East Asian (EAS) AF: 0.612 AC: 7220 AN: 11800

South Asian (SAS) AF: 0.598 AC: 21269 AN: 35568

European-Finnish (FIN) AF: 0.607 AC: 6625 AN: 10920

Middle Eastern (MID) AF: 0.524 AC: 485 AN: 926

European-Non Finnish (NFE) AF: 0.530 AC: 73970 AN: 139650

Other (OTH) AF: 0.569 AC: 7197 AN: 12654

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

African (AFR) AF: 0.906 AC: 37586 AN: 41474

American (AMR) AF: 0.569 AC: 8685 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3468

East Asian (EAS) AF: 0.613 AC: 3168 AN: 5168

South Asian (SAS) AF: 0.600 AC: 2897 AN: 4832

European-Finnish (FIN) AF: 0.628 AC: 6616 AN: 10538

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36292 AN: 67960

Other (OTH) AF: 0.611 AC: 1289 AN: 2110

Alfa AF: 0.583 Hom.: 6308

Bravo AF: 0.655

Asia WGS AF: 0.631 AC: 2192 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.46
PhyloP100		-0.47
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: rs1685356; hg19: chr11-73712859;