8-18400593-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000015.3(NAT2):c.590G>A(p.Arg197Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,612,574 control chromosomes in the GnomAD database, including 68,230 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,drug response (no stars).

Frequency

Genomes: 𝑓 0.27 ( 5830 hom., cov: 31)

Exomes 𝑓: 0.29 ( 62400 hom. )

Consequence

NAT2
NM_000015.3 missense

Scores

Clinical Significance

Benign; drug response no assertion criteria provided B:1O:1

Conservation

PhyloP100: 1.09

Publications

439 publications found

Variant links:

Genes affected

NAT2 (HGNC:7646): (N-acetyltransferase 2) This gene encodes an enzyme that functions to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism in which human populations segregate into rapid, intermediate, and slow acetylator phenotypes. Polymorphisms in this gene are also associated with higher incidences of cancer and drug toxicity. A second polymorphic arylamine N-acetyltransferase gene (NAT1), is located near this gene (NAT2). [provided by RefSeq, Sep 2019]

NAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.61936E-4).

BP6

Variant 8-18400593-G-A is Benign according to our data. Variant chr8-18400593-G-A is described in ClinVar as Benign|drug_response. ClinVar VariationId is 722.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000015.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT2	NM_000015.3	MANE Select	c.590G>A	p.Arg197Gln	missense	Exon 2 of 2	NP_000006.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT2	ENST00000286479.4	TSL:1 MANE Select	c.590G>A	p.Arg197Gln	missense	Exon 2 of 2	ENSP00000286479.3
	NAT2	ENST00000520116.1	TSL:3	c.200G>A	p.Arg67Gln	missense	Exon 2 of 2	ENSP00000428416.1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41457

AN:

151716

Hom.:

5835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.274

GnomAD2 exomes

AF:

0.273

AC:

68188

AN:

249910

AF XY:

0.282

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.289

AC:

422623

AN:

1460740

Hom.:

62400

Cov.:

AF XY:

0.292

AC XY:

212083

AN XY:

726624

show subpopulations

African (AFR)

AF:

0.257

AC:

8593

AN:

33408

American (AMR)

AF:

0.160

AC:

7136

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

9477

AN:

26070

East Asian (EAS)

AF:

0.222

AC:

8817

AN:

39696

South Asian (SAS)

AF:

0.359

AC:

30877

AN:

85914

European-Finnish (FIN)

AF:

0.240

AC:

12816

AN:

53316

Middle Eastern (MID)

AF:

0.286

AC:

1647

AN:

5754

European-Non Finnish (NFE)

AF:

0.293

AC:

325416

AN:

1111648

Other (OTH)

AF:

0.296

AC:

17844

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16416

32832

49248

65664

82080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10804

21608

32412

43216

54020

<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

AF:

0.273

AC:

41450

AN:

151834

Hom.:

5830

Cov.:

AF XY:

0.270

AC XY:

20060

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.258

AC:

10698

AN:

41392

American (AMR)

AF:

0.207

AC:

3153

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1253

AN:

3466

East Asian (EAS)

AF:

0.257

AC:

1323

AN:

5154

South Asian (SAS)

AF:

0.363

AC:

1749

AN:

4812

European-Finnish (FIN)

AF:

0.234

AC:

2458

AN:

10502

Middle Eastern (MID)

AF:

0.277

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.292

AC:

19841

AN:

67936

Other (OTH)

AF:

0.271

AC:

572

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1543

3087

4630

6174

7717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.282

Hom.:

30268

Bravo

AF:

0.264

TwinsUK

AF:

0.290

AC:

1076

ALSPAC

AF:

0.303

AC:

1168

ESP6500AA

AF:

0.266

AC:

1171

ESP6500EA

AF:

0.290

AC:

2497

ExAC

AF:

0.277

AC:

33610

Asia WGS

AF:

0.314

AC:

1091

AN:

3478

EpiCase

AF:

0.294

EpiControl

AF:

0.294

ClinVar

Significance: Benign; drug response

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NAT2-related disorder

Benign:1

Mar 29, 2023

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Slow acetylator due to N-acetyltransferase enzyme variant

Other:1

Oct 28, 2012

OMIM

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0094

Eigen

Benign

0.088

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.83

MetaRNN

Benign

0.00046

MetaSVM

Benign

-0.94

PhyloP100

1.1

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.17

Sift

Benign

0.054

Sift4G

Benign

0.091

Polyphen

1.0

Vest4

0.082

MPC

0.0095

ClinPred

0.042

GERP RS

2.5

gMVP

0.69

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over