Genetic Variant NAT1:p.Asp251Val (chr8-18222799-A-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000662.8(NAT1):c.752A>T(p.Asp251Val) variant causes a missense change. The variant allele was found at a frequency of 0.00274 in 1,612,508 control chromosomes in the GnomAD database, including 11 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 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 10 hom. )

Consequence

NAT1
NM_000662.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.27

Publications

40 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014334112).

BS2

High AC in GnomAd4 at 361 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.752A>T	p.Asp251Val	missense	Exon 3 of 3	NP_000653.3
NAT1	NM_001160175.4		c.938A>T	p.Asp313Val	missense	Exon 5 of 5	NP_001153647.1	F5H5R8
NAT1	NM_001160176.4		c.938A>T	p.Asp313Val	missense	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.752A>T	p.Asp251Val	missense	Exon 3 of 3	ENSP00000307218.4	P18440
NAT1	ENST00000518029.5	TSL:1	c.752A>T	p.Asp251Val	missense	Exon 4 of 4	ENSP00000428270.1	P18440
NAT1	ENST00000545197.3	TSL:5	c.938A>T	p.Asp313Val	missense	Exon 4 of 4	ENSP00000443194.1	F5H5R8

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

361

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00335

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00241

AC:

603

AN:

249820

AF XY:

0.00246

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.000995

Gnomad ASJ exome

AF:

0.000700

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00723

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00278

AC:

4065

AN:

1460196

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

1988

AN XY:

726204

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33416

American (AMR)

AF:

0.00112

AC:

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.000729

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.000210

AC:

AN:

85682

European-Finnish (FIN)

AF:

0.00714

AC:

381

AN:

53374

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00309

AC:

3439

AN:

1111424

Other (OTH)

AF:

0.00234

AC:

141

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

214

429

643

858

1072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<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:

0.00237

AC:

361

AN:

152312

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41568

American (AMR)

AF:

0.00137

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00706

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00335

AC:

228

AN:

68014

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00266

Hom.:

Bravo

AF:

0.00202

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00241

AC:

292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.028

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.1

PhyloP100

6.3

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-6.6

REVEL

Benign

0.26

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.59

MVP

0.54

MPC

0.12

ClinPred

0.041

GERP RS

4.2

Varity_R

0.87

gMVP

0.77

Mutation Taster

=84/16

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