chr11-62671995-A-G

Variant names:

• chr11-62671995-A-G
• rs753944461
• NM_001085372.3:c.163A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

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=0.12309575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCC3	NM_001085372.3	c.163A>G	p.Arg55Gly	missense_variant	Exon 2 of 2	ENST00000377953.4	NP_001078841.1
LBHD1	NM_024099.5	c.-442T>C		5_prime_UTR_variant	Exon 1 of 7	ENST00000354588.8	NP_077004.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCC3	ENST00000377953.4	c.163A>G	p.Arg55Gly	missense_variant	Exon 2 of 2	1	NM_001085372.3	ENSP00000367189.3
LBHD1	ENST00000354588.8	c.-442T>C		5_prime_UTR_variant	Exon 1 of 7	1	NM_024099.5	ENSP00000346600.3

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 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

Other links and lift over

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