11-62672065-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000377953.4(UQCC3):ā€‹c.233A>Gā€‹(p.Lys78Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,608,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

UQCC3
ENST00000377953.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68
Variant links:
Genes affected
UQCC3 (HGNC:34399): (ubiquinol-cytochrome c reductase complex assembly factor 3) Complex III is a mitochondrial inner membrane protein complex that transfers electrons from ubiquinol to cytochrome c. This gene encodes a protein that functions in complex III assembly. Mutations in this gene result in Mitochondrial complex III deficiency, nuclear type 9. [provided by RefSeq, Dec 2014]
LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03413236).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UQCC3NM_001085372.3 linkuse as main transcriptc.233A>G p.Lys78Arg missense_variant 2/2 ENST00000377953.4 NP_001078841.1
LBHD1NM_024099.5 linkuse as main transcriptc.-512T>C 5_prime_UTR_variant 1/7 ENST00000354588.8 NP_077004.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UQCC3ENST00000377953.4 linkuse as main transcriptc.233A>G p.Lys78Arg missense_variant 2/21 NM_001085372.3 ENSP00000367189 P1
LBHD1ENST00000354588.8 linkuse as main transcriptc.-512T>C 5_prime_UTR_variant 1/71 NM_024099.5 ENSP00000346600 P1Q9BQE6-2
UQCC3ENST00000531323.1 linkuse as main transcriptc.233A>G p.Lys78Arg missense_variant 3/33 ENSP00000432692 P1
LBHD1ENST00000528862.2 linkuse as main transcriptc.93+62T>C intron_variant 3 ENSP00000434489

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00155
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000108
AC:
25
AN:
232478
Hom.:
0
AF XY:
0.0000946
AC XY:
12
AN XY:
126822
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00146
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1456138
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
723936
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000379
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00155
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000680
ExAC
AF:
0.0000495
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 27, 2023This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 78 of the UQCC3 protein (p.Lys78Arg). This variant is present in population databases (rs760613205, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with UQCC3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
T;T
Eigen
Benign
-0.083
Eigen_PC
Benign
-0.066
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.61
.;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.034
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.99
N;N
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.066
Sift
Benign
0.17
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.56
P;P
Vest4
0.13
MutPred
0.29
Loss of methylation at K78 (P = 0.0043);Loss of methylation at K78 (P = 0.0043);
MVP
0.15
MPC
0.61
ClinPred
0.19
T
GERP RS
4.0
Varity_R
0.085
gMVP
0.096

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: rs760613205; hg19: chr11-62439537; API