Genetic Variant NM_000015.3:c.*148T>C (chr8-18401024-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000015.3(NAT2):c.*148T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 534,638 control chromosomes in the GnomAD database, including 484 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 0.032 ( 96 hom., cov: 33)

Exomes 𝑓: 0.040 ( 388 hom. )

Consequence

NAT2
NM_000015.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.545

Publications

11 publications found

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]

NAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	NM_000015.3 link	c.*148T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2 link	c.*148T>C		3_prime_UTR_variant	Exon 3 of 3		XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4 link	c.*148T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_000015.3	ENSP00000286479.3
NAT2	ENST00000520116.1 link	c.*148T>C		downstream_gene_variant		3		ENSP00000428416.1

Frequencies

GnomAD3 genomes

AF:

0.0316

AC:

4815

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00898

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0498

GnomAD4 exome

AF:

0.0401

AC:

15321

AN:

382350

Hom.:

388

Cov.:

AF XY:

0.0399

AC XY:

7706

AN XY:

192912

show subpopulations

African (AFR)

AF:

0.00940

AC:

AN:

9042

American (AMR)

AF:

0.0298

AC:

282

AN:

9460

Ashkenazi Jewish (ASJ)

AF:

0.0347

AC:

368

AN:

10592

East Asian (EAS)

AF:

0.0000811

AC:

AN:

24656

South Asian (SAS)

AF:

0.0159

AC:

178

AN:

11190

European-Finnish (FIN)

AF:

0.0326

AC:

1243

AN:

38144

Middle Eastern (MID)

AF:

0.0619

AC:

101

AN:

1632

European-Non Finnish (NFE)

AF:

0.0477

AC:

12224

AN:

256320

Other (OTH)

AF:

0.0393

AC:

838

AN:

21314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

745

1490

2234

2979

3724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<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:

0.0316

AC:

4815

AN:

152288

Hom.:

Cov.:

AF XY:

0.0298

AC XY:

2218

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00902

AC:

375

AN:

41568

American (AMR)

AF:

0.0351

AC:

536

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0438

AC:

152

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0126

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0290

AC:

308

AN:

10620

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0473

AC:

3220

AN:

68014

Other (OTH)

AF:

0.0498

AC:

105

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

251

501

752

1002

1253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0402

Hom.:

211

Bravo

AF:

0.0317

Asia WGS

AF:

0.00578

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.55

PhyloP100

-0.55

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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