rs1799931

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000015(NAT2):c.857G>A(p.Gly286Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 152096 control chromosomes in the gnomAD Genomes database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.041 ( 227 hom., cov: 33)

Exomes 𝑓: 0.058 ( 682 hom. )

Consequence

NAT2
NM_000015 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -1.92

Links

NAT2 (HGNC:7646):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016905367).

BA1

GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT2	NM_000015.3 linkuse as main transcript	c.857G>A	p.Gly286Glu	missense_variant	2/2	ENST00000286479.4
NAT2	XM_017012938.2 linkuse as main transcript	c.857G>A	p.Gly286Glu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT2	ENST00000286479.4 linkuse as main transcript	c.857G>A	p.Gly286Glu	missense_variant	2/2	1	NM_000015.3	P1
NAT2	ENST00000520116.1 linkuse as main transcript	c.467G>A	p.Gly156Glu	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6284

AN:

152096

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0331

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0958

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.0478

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0545

GnomAD3 exomes

AF:

0.0576

AC:

13017

AN:

226094

Hom.:

682

AF XY:

0.0539

AC XY:

6612

AN XY:

122612

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.155

Gnomad SAS exome

AF:

0.0689

Gnomad FIN exome

AF:

0.0367

Gnomad NFE exome

AF:

0.0250

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0338

AC:

48617

AN:

1439998

Hom.:

1463

AF XY:

0.0341

AC XY:

24432

AN XY:

715712

show subpopulations

Gnomad4 AFR exome

AF:

0.0293

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.0690

Gnomad4 FIN exome

AF:

0.0370

Gnomad4 NFE exome

AF:

0.0239

Gnomad4 OTH exome

AF:

0.0409

Alfa

AF:

0.0307

Hom.:

269

Bravo

AF:

0.0470

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0197

AC:

ESP6500AA

AF:

0.0288

AC:

126

ESP6500EA

AF:

0.0199

AC:

170

ExAC

AF:

0.0520

AC:

6297

Asia WGS

AF:

0.106

AC:

367

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Slow acetylator due to N-acetyltransferase enzyme variant

Other:1

drug response, no assertion criteria provided

literature only

OMIM

Oct 28, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

Cadd

Benign

0.0070

Dann

Benign

0.29

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.036

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.022

Sift

Benign

0.48

T;T

Sift4G

Benign

0.97

T;T

Polyphen

0.32

B;.

Vest4

0.11

MPC

0.0041

ClinPred

0.0054

GERP RS

-5.1

gMVP

0.65

Splicing

Find out SpliceAI 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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over