dbSNP rs5030839: NAT1:p.Arg187* (chr8-18222606-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000662.8(NAT1):c.559C>T(p.Arg187*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,612,750 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 15 hom. )

Consequence

NAT1
NM_000662.8 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.463

Publications

54 publications found

Variant links:

Genes affected

NAT1 (HGNC:7645): (N-acetyltransferase 1) This gene is one of two arylamine N-acetyltransferase (NAT) genes in the human genome, and is orthologous to the mouse and rat Nat2 genes. The enzyme encoded by this gene catalyzes the transfer of an acetyl group from acetyl-CoA to various arylamine and hydrazine substrates. This enzyme helps metabolize drugs and other xenobiotics, and functions in folate catabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

NAT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 335 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAT1	NM_000662.8	MANE Select	c.559C>T	p.Arg187*	stop_gained	Exon 3 of 3	NP_000653.3
NAT1	NM_001160175.4		c.745C>T	p.Arg249*	stop_gained	Exon 5 of 5	NP_001153647.1	F5H5R8
NAT1	NM_001160176.4		c.745C>T	p.Arg249*	stop_gained	Exon 4 of 4	NP_001153648.1	F5H5R8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAT1	ENST00000307719.9	TSL:1 MANE Select	c.559C>T	p.Arg187*	stop_gained	Exon 3 of 3	ENSP00000307218.4	P18440
NAT1	ENST00000518029.5	TSL:1	c.559C>T	p.Arg187*	stop_gained	Exon 4 of 4	ENSP00000428270.1	P18440
NAT1	ENST00000545197.3	TSL:5	c.745C>T	p.Arg249*	stop_gained	Exon 4 of 4	ENSP00000443194.1	F5H5R8

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00298

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00241

AC:

602

AN:

249942

AF XY:

0.00235

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00291

Gnomad ASJ exome

AF:

0.00251

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.00545

GnomAD4 exome

AF:

0.00228

AC:

3329

AN:

1460518

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

1687

AN XY:

726506

show subpopulations

African (AFR)

AF:

0.00210

AC:

AN:

33388

American (AMR)

AF:

0.00321

AC:

143

AN:

44482

Ashkenazi Jewish (ASJ)

AF:

0.00234

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.000430

AC:

AN:

86030

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00975

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00248

AC:

2757

AN:

1111464

Other (OTH)

AF:

0.00327

AC:

197

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

202

404

605

807

1009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.00220

AC:

335

AN:

152232

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41532

American (AMR)

AF:

0.00307

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00299

AC:

203

AN:

68006

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00290

Hom.:

Bravo

AF:

0.00274

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00268

AC:

326

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00425

EpiControl

AF:

0.00510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.0031

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Benign

0.96

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.032

PhyloP100

0.46

Vest4

0.83

GERP RS

-0.58

Mutation Taster

=184/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over