dbSNP rs4986990: NAT1:p.Thr153Thr (chr8-18222506-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000662.8(NAT1):c.459G>A(p.Thr153Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,613,978 control chromosomes in the GnomAD database, including 485 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 0.018 ( 49 hom., cov: 32)

Exomes 𝑓: 0.022 ( 436 hom. )

Consequence

NAT1
NM_000662.8 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.751

Publications

27 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=-0.751 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8 link	c.459G>A	p.Thr153Thr	synonymous_variant	Exon 3 of 3	ENST00000307719.9	NP_000653.3	P18440

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9 link	c.459G>A	p.Thr153Thr	synonymous_variant	Exon 3 of 3	1	NM_000662.8	ENSP00000307218.4		P18440

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2757

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00491

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00674

Gnomad SAS

AF:

0.0357

Gnomad FIN

AF:

0.00887

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0203

AC:

5107

AN:

251132

AF XY:

0.0217

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.0426

Gnomad EAS exome

AF:

0.00794

Gnomad FIN exome

AF:

0.00864

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0289

GnomAD4 exome

AF:

0.0218

AC:

31925

AN:

1461824

Hom.:

436

Cov.:

AF XY:

0.0224

AC XY:

16291

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00505

AC:

169

AN:

33472

American (AMR)

AF:

0.0115

AC:

516

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0445

AC:

1164

AN:

26132

East Asian (EAS)

AF:

0.00587

AC:

233

AN:

39698

South Asian (SAS)

AF:

0.0270

AC:

2327

AN:

86256

European-Finnish (FIN)

AF:

0.00957

AC:

511

AN:

53416

Middle Eastern (MID)

AF:

0.0801

AC:

462

AN:

5768

European-Non Finnish (NFE)

AF:

0.0224

AC:

24912

AN:

1111976

Other (OTH)

AF:

0.0270

AC:

1631

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

1789

3577

5366

7154

8943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.0182

AC:

2765

AN:

152154

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1298

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00494

AC:

205

AN:

41492

American (AMR)

AF:

0.0148

AC:

226

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3468

East Asian (EAS)

AF:

0.00675

AC:

AN:

5184

South Asian (SAS)

AF:

0.0364

AC:

175

AN:

4814

European-Finnish (FIN)

AF:

0.00887

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0255

AC:

1736

AN:

67996

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

148

295

443

590

738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0246

Hom.:

277

Bravo

AF:

0.0174

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.1

(source)

DANN

Benign

0.47

PhyloP100

-0.75

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over