rs1799930

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,drug response (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	NM_000015.3 link	c.590G>A	p.Arg197Gln	missense_variant	Exon 2 of 2	ENST00000286479.4	NP_000006.2	P11245A4Z6T7
NAT2	XM_017012938.2 link	c.590G>A	p.Arg197Gln	missense_variant	Exon 3 of 3		XP_016868427.1	P11245A4Z6T7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4 link	c.590G>A	p.Arg197Gln	missense_variant	Exon 2 of 2	1	NM_000015.3	ENSP00000286479.3		P11245
NAT2	ENST00000520116.1 link	c.200G>A	p.Arg67Gln	missense_variant	Exon 2 of 2	3		ENSP00000428416.1		E7EWF9

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

GnomAD3 exomes

AF:

0.273

AC:

68188

AN:

249910

Hom.:

9856

AF XY:

0.282

AC XY:

38067

AN XY:

135124

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 SAS exome

AF:

0.362

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

Gnomad4 AFR exome

AF:

0.257

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.273

AC:

41450

AN:

151834

Hom.:

5830

Cov.:

AF XY:

0.270

AC XY:

20060

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.362

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.363

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.292

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.283

Hom.:

15609

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0094

.;T

Eigen

Benign

0.088

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.00046

T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.17

Sift

Benign

0.054

T;T

Sift4G

Benign

0.091

T;D

Polyphen

1.0

D;.

Vest4

0.082

MPC

0.0095

ClinPred

0.042

GERP RS

2.5

gMVP

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over