chr11-62671995-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001085372.3(UQCC3):​c.163A>G​(p.Arg55Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

Frequency

Genomes: not found (cov: 32)

Consequence

UQCC3
NM_001085372.3 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12309575).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UQCC3NM_001085372.3 linkc.163A>G p.Arg55Gly missense_variant Exon 2 of 2 ENST00000377953.4 NP_001078841.1 Q6UW78
LBHD1NM_024099.5 linkc.-442T>C 5_prime_UTR_variant Exon 1 of 7 ENST00000354588.8 NP_077004.2 Q9BQE6-2A0A024R584

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UQCC3ENST00000377953.4 linkc.163A>G p.Arg55Gly missense_variant Exon 2 of 2 1 NM_001085372.3 ENSP00000367189.3 Q6UW78
LBHD1ENST00000354588.8 linkc.-442T>C 5_prime_UTR_variant Exon 1 of 7 1 NM_024099.5 ENSP00000346600.3 Q9BQE6-2
UQCC3ENST00000531323.1 linkc.163A>G p.Arg55Gly missense_variant Exon 3 of 3 3 ENSP00000432692.1 Q6UW78
LBHD1ENST00000528862.2 linkc.93+132T>C intron_variant Intron 1 of 2 3 ENSP00000434489.2 E9PQ29

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.163A>G (p.R55G) alteration is located in exon 2 (coding exon 2) of the UQCC3 gene. This alteration results from a A to G substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
16
DANN
Benign
0.92
DEOGEN2
Uncertain
0.62
D;D
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.094
N
LIST_S2
Benign
0.44
.;T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.0
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Benign
0.039
Sift
Uncertain
0.012
D;D
Sift4G
Uncertain
0.011
D;D
Polyphen
0.0010
B;B
Vest4
0.096
MutPred
0.22
Loss of MoRF binding (P = 0.0834);Loss of MoRF binding (P = 0.0834);
MVP
0.088
MPC
0.47
ClinPred
0.70
D
GERP RS
1.3
Varity_R
0.33
gMVP
0.13

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: rs753944461; hg19: chr11-62439467; COSMIC: COSV53656661; COSMIC: COSV53656661; API