6-3010156-C-G

Position:

• chr6-3010156-C-G

Variant summary

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

The NM_000904.6(NQO2):​c.139C>G​(p.Leu47Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L47F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NQO2 NM_000904.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02

Genes affected

NQO2 (HGNC:7856): (N-ribosyldihydronicotinamide:quinone dehydrogenase 2) This gene encodes a member of the thioredoxin family of enzymes. It is a cytosolic and ubiquitously expressed flavoprotein that catalyzes the two-electron reduction of quinone substrates and uses dihydronicotinamide riboside as a reducing coenzyme. Mutations in this gene have been associated with neurodegenerative diseases and several cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

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=0.21437886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NQO2	NM_000904.6	c.139C>G	p.Leu47Val	missense_variant	3/7	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2	c.139C>G	p.Leu47Val	missense_variant	6/10		NP_001277150.1
NQO2	NM_001318940.2	c.139C>G	p.Leu47Val	missense_variant	3/7		NP_001305869.1
NQO2	NM_001290222.2	c.139C>G	p.Leu47Val	missense_variant	3/6		NP_001277151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11	c.139C>G	p.Leu47Val	missense_variant	3/7	1	NM_000904.6	ENSP00000369822.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	.;.;.;T;.;T;.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D;.;D;.;.;.;D;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.090	.;.;.;N;.;N;.;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.020	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D;D;D;D;D
Polyphen		0.0050	.;.;.;B;.;B;.;B
Vest4		0.21, 0.29, 0.21
MutPred		0.54		Gain of catalytic residue at L47 (P = 0.0738);Gain of catalytic residue at L47 (P = 0.0738);Gain of catalytic residue at L47 (P = 0.0738);Gain of catalytic residue at L47 (P = 0.0738);Gain of catalytic residue at L47 (P = 0.0738);Gain of catalytic residue at L47 (P = 0.0738);Gain of catalytic residue at L47 (P = 0.0738);Gain of catalytic residue at L47 (P = 0.0738);
MVP		0.22
MPC		0.093
ClinPred		0.69	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.77
gMVP		0.65

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: rs1143684; hg19: chr6-3010390;