chr11-74003826-C-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_003356.4(UCP3):c.824+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,594,040 control chromosomes in the GnomAD database, including 313 homozygotes. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.025 ( 166 hom., cov: 33)
Exomes 𝑓: 0.0027 ( 147 hom. )
Consequence
UCP3
NM_003356.4 splice_donor
NM_003356.4 splice_donor
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 7.71
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 11-74003826-C-T is Benign according to our data. Variant chr11-74003826-C-T is described in ClinVar as [Benign]. Clinvar id is 7578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0856 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UCP3 | NM_003356.4 | c.824+1G>A | splice_donor_variant | ENST00000314032.9 | |||
UCP3 | XM_047427519.1 | c.824+1G>A | splice_donor_variant | ||||
UCP3 | NM_022803.3 | c.825G>A | p.Gly275= | synonymous_variant | 6/6 | ||
UCP3 | XR_007062495.1 | n.1028G>A | non_coding_transcript_exon_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UCP3 | ENST00000314032.9 | c.824+1G>A | splice_donor_variant | 1 | NM_003356.4 | P1 | |||
UCP3 | ENST00000426995.2 | c.825G>A | p.Gly275= | synonymous_variant | 6/6 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0254 AC: 3873AN: 152184Hom.: 166 Cov.: 33
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GnomAD3 exomes AF: 0.00657 AC: 1559AN: 237186Hom.: 54 AF XY: 0.00471 AC XY: 602AN XY: 127790
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GnomAD4 exome AF: 0.00266 AC: 3837AN: 1441738Hom.: 147 Cov.: 31 AF XY: 0.00237 AC XY: 1697AN XY: 715230
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GnomAD4 genome AF: 0.0255 AC: 3883AN: 152302Hom.: 166 Cov.: 33 AF XY: 0.0243 AC XY: 1810AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2019 | This variant is associated with the following publications: (PMID: 9769326, 25525159, 22344438, 10618503) - |
Morbid obesity Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1998 | - - |
UCP3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 29, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
UCP3 POLYMORPHISM, EXON 6 SPLICE DONOR JUNCTION Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Oct 01, 1998 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
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Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at