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rs1799930

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.27 ( 5830 hom., cov: 31)
Exomes 𝑓: 0.29 ( 62400 hom. )

Consequence

NAT2
NM_000015.3 missense

Scores

1
1
14

Clinical Significance

Benign criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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]. Clinvar id is 722.Status of the report is criteria_provided_single_submitter, 1 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/exons MANE UniProt
NAT2NM_000015.3 linkuse as main transcriptc.590G>A p.Arg197Gln missense_variant 2/2 ENST00000286479.4
NAT2XM_017012938.2 linkuse as main transcriptc.590G>A p.Arg197Gln missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAT2ENST00000286479.4 linkuse as main transcriptc.590G>A p.Arg197Gln missense_variant 2/21 NM_000015.3 P1
NAT2ENST00000520116.1 linkuse as main transcriptc.200G>A p.Arg67Gln missense_variant 2/23

Frequencies

GnomAD3 genomes
AF:
0.273
AC:
41457
AN:
151716
Hom.:
5835
Cov.:
31
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.:
48
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.:
31
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
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

NAT2-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 29, 2023This 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
drug response, no assertion criteria providedliterature onlyOMIMOct 28, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.42
Cadd
Benign
22
Dann
Pathogenic
1.0
Eigen
Benign
0.088
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.83
T;T
MetaRNN
Benign
0.00046
T;T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
0.0016
P;P
PrimateAI
Benign
0.24
T
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
T
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.

Other links and lift over

dbSNP: rs1799930; hg19: chr8-18258103; COSMIC: COSV54061522; API