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rs1041983

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000015.3(NAT2):c.282C>T(p.Tyr94=) 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 (★).

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 criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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 criteria_provided_single_submitter, 1 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/exons MANE UniProt
NAT2NM_000015.3 linkuse as main transcriptc.282C>T p.Tyr94= synonymous_variant 2/2 ENST00000286479.4
NAT2XM_017012938.2 linkuse as main transcriptc.282C>T p.Tyr94= synonymous_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAT2ENST00000286479.4 linkuse as main transcriptc.282C>T p.Tyr94= synonymous_variant 2/21 NM_000015.3 P1
NAT2ENST00000520116.1 linkuse as main transcriptc.-57-52C>T intron_variant 3

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
GnomAD3 exomes
AF:
0.342
AC:
85599
AN:
250306
Hom.:
15264
AF XY:
0.344
AC XY:
46546
AN XY:
135260
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 SAS exome
AF:
0.428
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
Gnomad4 AMR exome
AF:
0.307
Gnomad4 ASJ exome
AF:
0.382
Gnomad4 EAS exome
AF:
0.352
Gnomad4 SAS exome
AF:
0.428
Gnomad4 FIN exome
AF:
0.278
Gnomad4 NFE exome
AF:
0.317
Gnomad4 OTH exome
AF:
0.347
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
Gnomad4 AMR
AF:
0.321
Gnomad4 ASJ
AF:
0.382
Gnomad4 EAS
AF:
0.413
Gnomad4 SAS
AF:
0.437
Gnomad4 FIN
AF:
0.267
Gnomad4 NFE
AF:
0.318
Gnomad4 OTH
AF:
0.363
Alfa
AF:
0.327
Hom.:
17518
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: 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). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.48
Dann
Benign
0.28

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