Variant 6-3010156-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000904.6(NQO2):c.139C>T(p.Leu47Phe) variant causes a missense change. The variant allele was found at a frequency of 0.795 in 1,611,640 control chromosomes in the GnomAD database, including 512,037 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.83 ( 53360 hom., cov: 31)

Exomes 𝑓: 0.79 ( 458677 hom. )

Consequence

NQO2
NM_000904.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.02

Variant links:

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]

NQO2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.272047E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NQO2	NM_000904.6 linkuse as main transcript	c.139C>T	p.Leu47Phe	missense_variant	3/7	ENST00000380455.11	NP_000895.2
NQO2	NM_001290221.2 linkuse as main transcript	c.139C>T	p.Leu47Phe	missense_variant	6/10		NP_001277150.1
NQO2	NM_001318940.2 linkuse as main transcript	c.139C>T	p.Leu47Phe	missense_variant	3/7		NP_001305869.1
NQO2	NM_001290222.2 linkuse as main transcript	c.139C>T	p.Leu47Phe	missense_variant	3/6		NP_001277151.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NQO2	ENST00000380455.11 linkuse as main transcript	c.139C>T	p.Leu47Phe	missense_variant	3/7	1	NM_000904.6	ENSP00000369822.4		P16083

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126612

AN:

151912

Hom.:

53297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.956

Gnomad AMI

AF:

0.847

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.653

Gnomad SAS

AF:

0.731

Gnomad FIN

AF:

0.872

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.793

Gnomad OTH

AF:

0.798

GnomAD3 exomes

AF:

0.787

AC:

196615

AN:

249970

Hom.:

77920

AF XY:

0.782

AC XY:

105626

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.964

Gnomad AMR exome

AF:

0.784

Gnomad ASJ exome

AF:

0.707

Gnomad EAS exome

AF:

0.652

Gnomad SAS exome

AF:

0.737

Gnomad FIN exome

AF:

0.872

Gnomad NFE exome

AF:

0.788

Gnomad OTH exome

AF:

0.775

GnomAD4 exome

AF:

0.791

AC:

1154845

AN:

1459610

Hom.:

458677

Cov.:

AF XY:

0.789

AC XY:

572772

AN XY:

726064

show subpopulations

Gnomad4 AFR exome

AF:

0.965

Gnomad4 AMR exome

AF:

0.784

Gnomad4 ASJ exome

AF:

0.704

Gnomad4 EAS exome

AF:

0.624

Gnomad4 SAS exome

AF:

0.739

Gnomad4 FIN exome

AF:

0.872

Gnomad4 NFE exome

AF:

0.795

Gnomad4 OTH exome

AF:

0.786

GnomAD4 genome

AF:

0.834

AC:

126733

AN:

152030

Hom.:

53360

Cov.:

AF XY:

0.834

AC XY:

61975

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.957

Gnomad4 AMR

AF:

0.782

Gnomad4 ASJ

AF:

0.712

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.729

Gnomad4 FIN

AF:

0.872

Gnomad4 NFE

AF:

0.793

Gnomad4 OTH

AF:

0.799

Alfa

AF:

0.784

Hom.:

116874

Bravo

AF:

0.833

TwinsUK

AF:

0.788

AC:

2921

ALSPAC

AF:

0.791

AC:

3050

ESP6500AA

AF:

0.961

AC:

4234

ESP6500EA

AF:

0.782

AC:

6728

ExAC

AF:

0.790

AC:

95939

Asia WGS

AF:

0.695

AC:

2416

AN:

3478

EpiCase

AF:

0.767

EpiControl

AF:

0.774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.016

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.19

DEOGEN2

Benign

0.044

.;.;.;T;.;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.62

T;.;T;.;.;.;T;T

MetaRNN

Benign

6.3e-7

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-3.1

.;.;.;N;.;N;.;N

PrimateAI

Benign

0.45

PROVEAN

Benign

5.2

N;N;N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T;T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T

Polyphen

0.0

.;.;.;B;.;B;.;B

Vest4

0.087, 0.21, 0.20, 0.084

MPC

0.087

ClinPred

0.0079

GERP RS

5.6

Varity_R

0.40

gMVP

0.48

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over