6-3010156-C-T

Variant names:

• chr6-3010156-C-T
• rs1143684
• NM_000904.6:c.139C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 70 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000904.6. 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
	NQO2	NM_000904.6	MANE Select	c.139C>T	p.Leu47Phe	missense	Exon 3 of 7	NP_000895.2	P16083
	NQO2	NM_001290221.2		c.139C>T	p.Leu47Phe	missense	Exon 6 of 10	NP_001277150.1	P16083
	NQO2	NM_001318940.2		c.139C>T	p.Leu47Phe	missense	Exon 3 of 7	NP_001305869.1	P16083

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NQO2	ENST00000380455.11	TSL:1 MANE Select	c.139C>T	p.Leu47Phe	missense	Exon 3 of 7	ENSP00000369822.4	P16083
	NQO2	ENST00000952452.1		c.184C>T	p.Leu62Phe	missense	Exon 3 of 7	ENSP00000622511.1
	NQO2	ENST00000338130.7	TSL:2	c.139C>T	p.Leu47Phe	missense	Exon 6 of 10	ENSP00000337773.2	P16083

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

GnomAD2 exomes AF: 0.787 AC: 196615 AN: 249970 AF XY: 0.782

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 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

African (AFR) AF: 0.965 AC: 32267 AN: 33440

American (AMR) AF: 0.784 AC: 34855 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 18381 AN: 26094

East Asian (EAS) AF: 0.624 AC: 24742 AN: 39666

South Asian (SAS) AF: 0.739 AC: 63596 AN: 86038

European-Finnish (FIN) AF: 0.872 AC: 46564 AN: 53376

Middle Eastern (MID) AF: 0.763 AC: 4396 AN: 5762

European-Non Finnish (NFE) AF: 0.795 AC: 882642 AN: 1110486

Other (OTH) AF: 0.786 AC: 47402 AN: 60312

GnomAD4 genome AF: 0.834 AC: 126733 AN: 152030 Hom.: 53360 Cov.: 31 AF XY: 0.834 AC XY: 61975 AN XY: 74316

African (AFR) AF: 0.957 AC: 39701 AN: 41506

American (AMR) AF: 0.782 AC: 11941 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2469 AN: 3470

East Asian (EAS) AF: 0.653 AC: 3342 AN: 5118

South Asian (SAS) AF: 0.729 AC: 3505 AN: 4806

European-Finnish (FIN) AF: 0.872 AC: 9225 AN: 10576

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.793 AC: 53907 AN: 67974

Other (OTH) AF: 0.799 AC: 1685 AN: 2110

Alfa AF: 0.793 Hom.: 233139

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 v4.9

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
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	6.3e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-3.1	N
PhyloP100		5.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	5.2	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.087
MPC		0.087
ClinPred		0.0079	T
GERP RS		5.6
Varity_R		0.40
gMVP		0.48
Mutation Taster		=47/52	polymorphism (auto)

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