rs11235971

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003356.4(UCP3):​c.825-989A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,140 control chromosomes in the GnomAD database, including 3,966 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3966 hom., cov: 32)

Consequence

UCP3
NM_003356.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.800
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UCP3NM_003356.4 linkuse as main transcriptc.825-989A>G intron_variant ENST00000314032.9
UCP3XM_047427519.1 linkuse as main transcriptc.825-989A>G intron_variant
UCP3XR_007062495.1 linkuse as main transcriptn.2339A>G non_coding_transcript_exon_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UCP3ENST00000314032.9 linkuse as main transcriptc.825-989A>G intron_variant 1 NM_003356.4 P1P55916-1

Frequencies

GnomAD3 genomes
AF:
0.218
AC:
33165
AN:
152022
Hom.:
3970
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.157
Gnomad AMI
AF:
0.143
Gnomad AMR
AF:
0.149
Gnomad ASJ
AF:
0.214
Gnomad EAS
AF:
0.291
Gnomad SAS
AF:
0.243
Gnomad FIN
AF:
0.381
Gnomad MID
AF:
0.117
Gnomad NFE
AF:
0.241
Gnomad OTH
AF:
0.183
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.218
AC:
33167
AN:
152140
Hom.:
3966
Cov.:
32
AF XY:
0.224
AC XY:
16631
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.157
Gnomad4 AMR
AF:
0.149
Gnomad4 ASJ
AF:
0.214
Gnomad4 EAS
AF:
0.291
Gnomad4 SAS
AF:
0.243
Gnomad4 FIN
AF:
0.381
Gnomad4 NFE
AF:
0.241
Gnomad4 OTH
AF:
0.182
Alfa
AF:
0.224
Hom.:
6362
Bravo
AF:
0.194
Asia WGS
AF:
0.246
AC:
854
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.1
DANN
Benign
0.66

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11235971; hg19: chr11-73713560; API