11-62671974-A-G

Position:

• chr11-62671974-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000377953.4(UQCC3):​c.142A>G​(p.Arg48Gly) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R48K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UQCC3 ENST00000377953.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.943

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]

ACMG classification

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=0.11268422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCC3	NM_001085372.3	c.142A>G	p.Arg48Gly	missense_variant	2/2	ENST00000377953.4	NP_001078841.1
LBHD1	NM_024099.5	c.-421T>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
UQCC3	ENST00000377953.4	c.142A>G	p.Arg48Gly	missense_variant	2/2	1	NM_001085372.3	ENSP00000367189	P1
LBHD1	ENST00000354588.8	c.-421T>C		5_prime_UTR_variant	1/7	1	NM_024099.5	ENSP00000346600	P1
UQCC3	ENST00000531323.1	c.142A>G	p.Arg48Gly	missense_variant	3/3	3		ENSP00000432692	P1
LBHD1	ENST00000528862.2	c.93+153T>C		intron_variant		3		ENSP00000434489

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

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 17, 2023

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 48 of the UQCC3 protein (p.Arg48Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with UQCC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1944225). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.69
DEOGEN2	Uncertain	0.55	D;D
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.073
Sift	Benign	0.21	T;T
Sift4G	Uncertain	0.049	D;D
Polyphen		0.36	B;B
Vest4		0.14
MutPred		0.15		Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);
MVP		0.088
MPC		0.49
ClinPred		0.39	T
GERP RS		3.2
Varity_R		0.16
gMVP		0.072

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62439446;