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rs1799931

Variant summary

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

The NM_000015.3(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 0.0345 in 1,592,210 control chromosomes in the GnomAD database, including 1,691 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 ( 228 hom., cov: 33)
Exomes 𝑓: 0.034 ( 1463 hom. )

Consequence

NAT2
NM_000015.3 missense

Scores

16

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -1.92
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]

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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
GnomAd4 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
NAT2NM_000015.3 linkuse as main transcriptc.857G>A p.Gly286Glu missense_variant 2/2 ENST00000286479.4
NAT2XM_017012938.2 linkuse as main transcriptc.857G>A p.Gly286Glu missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAT2ENST00000286479.4 linkuse as main transcriptc.857G>A p.Gly286Glu missense_variant 2/21 NM_000015.3 P1
NAT2ENST00000520116.1 linkuse as main transcriptc.467G>A p.Gly156Glu missense_variant 2/23

Frequencies

GnomAD3 genomes
AF:
0.0413
AC:
6284
AN:
152096
Hom.:
227
Cov.:
33
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
Cov.:
32
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
GnomAD4 genome
AF:
0.0414
AC:
6297
AN:
152212
Hom.:
228
Cov.:
33
AF XY:
0.0446
AC XY:
3319
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0330
Gnomad4 AMR
AF:
0.0962
Gnomad4 ASJ
AF:
0.0205
Gnomad4 EAS
AF:
0.151
Gnomad4 SAS
AF:
0.0740
Gnomad4 FIN
AF:
0.0340
Gnomad4 NFE
AF:
0.0257
Gnomad4 OTH
AF:
0.0573
Alfa
AF:
0.0307
Hom.:
269
Bravo
AF:
0.0470
TwinsUK
AF:
0.0227
AC:
84
ALSPAC
AF:
0.0197
AC:
76
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 providedliterature onlyOMIMOct 28, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.75
T
BayesDel_noAF
Benign
-0.70
Cadd
Benign
0.0020
Dann
Benign
0.29
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0083
N
LIST_S2
Benign
0.036
T;T
MetaRNN
Benign
0.0017
T;T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.23
T
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
T
GERP RS
-5.1
gMVP
0.65

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.

Other links and lift over

dbSNP: rs1799931; hg19: chr8-18258370; COSMIC: COSV99673956; API