8-18400344-T-C

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.341T>C(p.Ile114Thr) variant causes a missense change. The variant allele was found at a frequency of 0.421 in 1,612,532 control chromosomes in the GnomAD database, including 148,423 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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 0.38 ( 11840 hom., cov: 29)

Exomes 𝑓: 0.42 ( 136583 hom. )

Consequence

NAT2
NM_000015.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.86

Publications

386 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=0.0032346249).

BP6

Variant 8-18400344-T-C is Benign according to our data. Variant chr8-18400344-T-C is described in ClinVar as Benign|drug_response. ClinVar VariationId is 723.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	NM_000015.3 link	c.341T>C	p.Ile114Thr	missense_variant	Exon 2 of 2	ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2 link	c.341T>C	p.Ile114Thr	missense_variant	Exon 3 of 3		XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
NAT2	ENST00000286479.4 link	c.341T>C	p.Ile114Thr	missense_variant	Exon 2 of 2	1	NM_000015.3	ENSP00000286479.3
NAT2	ENST00000520116.1 link	c.-50T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 2	3		ENSP00000428416.1
NAT2	ENST00000520116.1 link	c.-50T>C		5_prime_UTR_variant	Exon 2 of 2	3		ENSP00000428416.1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

57850

AN:

151550

Hom.:

11834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.0365

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.395

GnomAD2 exomes

AF:

0.381

AC:

95254

AN:

250338

AF XY:

0.386

show subpopulations

Gnomad AFR exome

AF:

0.304

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.0384

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.454

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.425

AC:

620630

AN:

1460862

Hom.:

136583

Cov.:

AF XY:

0.424

AC XY:

308238

AN XY:

726712

show subpopulations

African (AFR)

AF:

0.306

AC:

10240

AN:

33428

American (AMR)

AF:

0.313

AC:

13984

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

11539

AN:

26030

East Asian (EAS)

AF:

0.0268

AC:

1062

AN:

39692

South Asian (SAS)

AF:

0.345

AC:

29744

AN:

86144

European-Finnish (FIN)

AF:

0.459

AC:

24521

AN:

53378

Middle Eastern (MID)

AF:

0.453

AC:

2612

AN:

5760

European-Non Finnish (NFE)

AF:

0.452

AC:

502336

AN:

1111472

Other (OTH)

AF:

0.408

AC:

24592

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

19811

39622

59432

79243

99054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14794

29588

44382

59176

73970

<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:

0.382

AC:

57876

AN:

151670

Hom.:

11840

Cov.:

AF XY:

0.379

AC XY:

28069

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.305

AC:

12594

AN:

41348

American (AMR)

AF:

0.353

AC:

5367

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1549

AN:

3462

East Asian (EAS)

AF:

0.0366

AC:

188

AN:

5142

South Asian (SAS)

AF:

0.339

AC:

1629

AN:

4800

European-Finnish (FIN)

AF:

0.469

AC:

4922

AN:

10492

Middle Eastern (MID)

AF:

0.459

AC:

134

AN:

292

European-Non Finnish (NFE)

AF:

0.447

AC:

30341

AN:

67896

Other (OTH)

AF:

0.392

AC:

823

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1711

3421

5132

6842

8553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.422

Hom.:

45713

Bravo

AF:

0.370

TwinsUK

AF:

0.448

AC:

1661

ALSPAC

AF:

0.439

AC:

1691

ESP6500AA

AF:

0.298

AC:

1311

ESP6500EA

AF:

0.445

AC:

3831

ExAC

AF:

0.384

AC:

46624

Asia WGS

AF:

0.197

AC:

687

AN:

3478

EpiCase

AF:

0.446

EpiControl

AF:

0.445

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

Dec 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

0.086

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.93

PhyloP100

3.9

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.098

Sift

Benign

0.048

Sift4G

Uncertain

0.043

Vest4

0.12

ClinPred

0.064

GERP RS

0.54

gMVP

0.68

Mutation Taster

=76/24

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over