rs1041983

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000015.3(NAT2):​c.282C>T​(p.Tyr94Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,612,606 control chromosomes in the GnomAD database, including 90,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.36 ( 10196 hom., cov: 31)
Exomes 𝑓: 0.33 ( 80426 hom. )

Consequence

NAT2
NM_000015.3 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0750
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 8-18400285-C-T is Benign according to our data. Variant chr8-18400285-C-T is described in ClinVar as [Benign]. Clinvar id is 3060182.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.075 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAT2NM_000015.3 linkc.282C>T p.Tyr94Tyr synonymous_variant Exon 2 of 2 ENST00000286479.4 NP_000006.2 P11245A4Z6T7
NAT2XM_017012938.2 linkc.282C>T p.Tyr94Tyr synonymous_variant Exon 3 of 3 XP_016868427.1 P11245A4Z6T7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAT2ENST00000286479.4 linkc.282C>T p.Tyr94Tyr synonymous_variant Exon 2 of 2 1 NM_000015.3 ENSP00000286479.3 P11245
NAT2ENST00000520116.1 linkc.-57-52C>T intron_variant Intron 1 of 1 3 ENSP00000428416.1 E7EWF9

Frequencies

GnomAD3 genomes
AF:
0.360
AC:
54604
AN:
151710
Hom.:
10194
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.450
Gnomad AMI
AF:
0.355
Gnomad AMR
AF:
0.321
Gnomad ASJ
AF:
0.382
Gnomad EAS
AF:
0.412
Gnomad SAS
AF:
0.439
Gnomad FIN
AF:
0.267
Gnomad MID
AF:
0.334
Gnomad NFE
AF:
0.318
Gnomad OTH
AF:
0.362
GnomAD2 exomes
AF:
0.342
AC:
85599
AN:
250306
AF XY:
0.344
show subpopulations
Gnomad AFR exome
AF:
0.449
Gnomad AMR exome
AF:
0.304
Gnomad ASJ exome
AF:
0.372
Gnomad EAS exome
AF:
0.419
Gnomad FIN exome
AF:
0.274
Gnomad NFE exome
AF:
0.313
Gnomad OTH exome
AF:
0.330
GnomAD4 exome
AF:
0.328
AC:
479746
AN:
1460778
Hom.:
80426
Cov.:
39
AF XY:
0.331
AC XY:
240168
AN XY:
726604
show subpopulations
Gnomad4 AFR exome
AF:
0.455
AC:
15207
AN:
33440
Gnomad4 AMR exome
AF:
0.307
AC:
13676
AN:
44610
Gnomad4 ASJ exome
AF:
0.382
AC:
9933
AN:
26034
Gnomad4 EAS exome
AF:
0.352
AC:
13979
AN:
39686
Gnomad4 SAS exome
AF:
0.428
AC:
36886
AN:
86088
Gnomad4 FIN exome
AF:
0.278
AC:
14821
AN:
53382
Gnomad4 NFE exome
AF:
0.317
AC:
352389
AN:
1111452
Gnomad4 Remaining exome
AF:
0.347
AC:
20919
AN:
60328
Heterozygous variant carriers
0
18172
36344
54515
72687
90859
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
11728
23456
35184
46912
58640
<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:
0.360
AC:
54628
AN:
151828
Hom.:
10196
Cov.:
31
AF XY:
0.359
AC XY:
26637
AN XY:
74218
show subpopulations
Gnomad4 AFR
AF:
0.449
AC:
0.44942
AN:
0.44942
Gnomad4 AMR
AF:
0.321
AC:
0.320515
AN:
0.320515
Gnomad4 ASJ
AF:
0.382
AC:
0.382217
AN:
0.382217
Gnomad4 EAS
AF:
0.413
AC:
0.413001
AN:
0.413001
Gnomad4 SAS
AF:
0.437
AC:
0.437188
AN:
0.437188
Gnomad4 FIN
AF:
0.267
AC:
0.267356
AN:
0.267356
Gnomad4 NFE
AF:
0.318
AC:
0.317857
AN:
0.317857
Gnomad4 OTH
AF:
0.363
AC:
0.362512
AN:
0.362512
Heterozygous variant carriers
0
1733
3467
5200
6934
8667
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
538
1076
1614
2152
2690
<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:
0.331
Hom.:
35154
Bravo
AF:
0.363
Asia WGS
AF:
0.432
AC:
1503
AN:
3478
EpiCase
AF:
0.319
EpiControl
AF:
0.318

ClinVar

Significance: Benign
Submissions summary: Benign: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). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.48
DANN
Benign
0.28
Mutation Taster
=100/0
polymorphism (auto)

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: rs1041983; hg19: chr8-18257795; COSMIC: COSV54061508; API