dbSNP rs372417414: NQO1:p.Ter275Serext*? (chr16-69710977-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4

The NM_000903.3(NQO1):c.824G>C(p.Ter275Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,455,750 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. Synonymous variant affecting the same amino acid position has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

NQO1
NM_000903.3 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.692

Publications

0 publications found

Variant links:

Genes affected

NQO1 (HGNC:2874): (NAD(P)H quinone dehydrogenase 1) This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein's enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer's disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

NQO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Stoplost variant in NM_000903.3 Downstream stopcodon found after 98 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000903.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NQO1	NM_000903.3	MANE Select	c.824G>C	p.Ter275Serext*?	stop_lost	Exon 6 of 6	NP_000894.1	P15559-1
NQO1	NM_001025433.2		c.722G>C	p.Ter241Serext*?	stop_lost	Exon 5 of 5	NP_001020604.1	P15559-2
NQO1	NM_001025434.2		c.710G>C	p.Ter237Serext*?	stop_lost	Exon 5 of 5	NP_001020605.1	P15559-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NQO1	ENST00000320623.10	TSL:1 MANE Select	c.824G>C	p.Ter275Serext*?	stop_lost	Exon 6 of 6	ENSP00000319788.5	P15559-1
NQO1	ENST00000564043.1	TSL:1	c.761G>C	p.Ter254Serext*?	stop_lost	Exon 6 of 6	ENSP00000455020.1	H3BNV2
NQO1	ENST00000379047.7	TSL:1	c.722G>C	p.Ter241Serext*?	stop_lost	Exon 5 of 5	ENSP00000368335.3	P15559-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1455750

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33082

American (AMR)

AF:

0.00

AC:

AN:

43842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25946

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.00

AC:

AN:

85528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00000992

AC:

AN:

1108578

Other (OTH)

AF:

0.00

AC:

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.5

(source)

DANN

Benign

0.58

Eigen

Benign

0.13

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.38

PhyloP100

0.69

Vest4

0.30

GERP RS

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over