6-3019637-C-T

Variant names:

• chr6-3019637-C-T
• rs772030191
• NM_000904.6:c.678C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000904.6(NQO2):​c.678C>T​(p.His226His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NQO2 NM_000904.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 0 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]

HTATSF1P2 (HGNC:38586): (HIV-1 Tat specific factor 1 pseudogene 2)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.978 with no splicing effect.

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.678C>T	p.His226His	synonymous	Exon 7 of 7	NP_000895.2	P16083
	NQO2	NM_001290221.2		c.678C>T	p.His226His	synonymous	Exon 10 of 10	NP_001277150.1	P16083
	NQO2	NM_001318940.2		c.678C>T	p.His226His	synonymous	Exon 7 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.678C>T	p.His226His	synonymous	Exon 7 of 7	ENSP00000369822.4	P16083
	NQO2	ENST00000952452.1		c.723C>T	p.His241His	synonymous	Exon 7 of 7	ENSP00000622511.1
	NQO2	ENST00000338130.7	TSL:2	c.678C>T	p.His226His	synonymous	Exon 10 of 10	ENSP00000337773.2	P16083

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457936 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725214

African (AFR) AF: 0.0000300 AC: 1 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109756

Other (OTH) AF: 0.00 AC: 0 AN: 60176

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.043
DANN	Benign	0.35
PhyloP100		-0.98

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: rs772030191; hg19: chr6-3019871;