NM_001085372.3:c.163A>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/19 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
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085372.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC3	NM_001085372.3	MANE Select	c.163A>G	p.Arg55Gly	missense	Exon 2 of 2	NP_001078841.1	Q6UW78
	LBHD1	NM_024099.5	MANE Select	c.-442T>C		5_prime_UTR	Exon 1 of 7	NP_077004.2
	LBHD1	NM_001394599.1		c.-248T>C		5_prime_UTR	Exon 1 of 7	NP_001381528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCC3	ENST00000377953.4	TSL:1 MANE Select	c.163A>G	p.Arg55Gly	missense	Exon 2 of 2	ENSP00000367189.3	Q6UW78
	LBHD1	ENST00000354588.8	TSL:1 MANE Select	c.-442T>C		5_prime_UTR	Exon 1 of 7	ENSP00000346600.3	Q9BQE6-2
	UQCC3	ENST00000531323.1	TSL:3	c.163A>G	p.Arg55Gly	missense	Exon 3 of 3	ENSP00000432692.1	Q6UW78

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.039
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.011	D
Polyphen		0.0010	B
Vest4		0.096
MutPred		0.22		Loss of MoRF binding (P = 0.0834)
MVP		0.088
MPC		0.47
ClinPred		0.70	D
GERP RS		1.3
PromoterAI		0.12	Neutral
Varity_R		0.33
gMVP		0.13
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

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