chr6-3010156-C-T

Position:

• chr6-3010156-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• 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 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	UniProt
NQO2	NM_000904.6	c.139C>T	p.Leu47Phe	missense_variant	3/7	ENST00000380455.11
NQO2	NM_001290221.2	c.139C>T	p.Leu47Phe	missense_variant	6/10
NQO2	NM_001318940.2	c.139C>T	p.Leu47Phe	missense_variant	3/7
NQO2	NM_001290222.2	c.139C>T	p.Leu47Phe	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NQO2	ENST00000380455.11	c.139C>T	p.Leu47Phe	missense_variant	3/7	1	NM_000904.6	P1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126612 AN: 151912 Hom.: 53297 Cov.: 31

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

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.: 38 AF XY: 0.789 AC XY: 572772 AN XY: 726064

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.: 31 AF XY: 0.834 AC XY: 61975 AN XY: 74316

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	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.19
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.052	N
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	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.45	T
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	T
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

Other links and lift over

dbSNP: rs1143684; hg19: chr6-3010390; COSMIC: COSV57643512;