Variant chr8-18222687-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000662.8(NAT1):c.640T>G(p.Ser214Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,613,962 control chromosomes in the GnomAD database, including 483 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.018 ( 49 hom., cov: 32)

Exomes 𝑓: 0.022 ( 434 hom. )

Consequence

NAT1
NM_000662.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0750

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032370389).

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/exons	MANE	UniProt
NAT1	NM_000662.8 linkuse as main transcript	c.640T>G	p.Ser214Ala	missense_variant	3/3	ENST00000307719.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000307719.9 linkuse as main transcript	c.640T>G	p.Ser214Ala	missense_variant	3/3	1	NM_000662.8	P1

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2749

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00480

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00655

Gnomad SAS

AF:

0.0356

Gnomad FIN

AF:

0.00876

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0203

AC:

5085

AN:

250998

Hom.:

AF XY:

0.0216

AC XY:

2934

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0421

Gnomad EAS exome

AF:

0.00789

Gnomad SAS exome

AF:

0.0274

Gnomad FIN exome

AF:

0.00865

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0289

GnomAD4 exome

AF:

0.0218

AC:

31883

AN:

1461680

Hom.:

434

Cov.:

AF XY:

0.0224

AC XY:

16275

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.0114

Gnomad4 ASJ exome

AF:

0.0444

Gnomad4 EAS exome

AF:

0.00587

Gnomad4 SAS exome

AF:

0.0269

Gnomad4 FIN exome

AF:

0.00957

Gnomad4 NFE exome

AF:

0.0224

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.0181

AC:

2757

AN:

152282

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1296

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00484

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.00657

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.00876

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0251

Hom.:

Bravo

AF:

0.0174

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0171

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0240

AC:

206

ExAC

AF:

0.0209

AC:

2539

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.3

DANN

Benign

0.20

DEOGEN2

Benign

0.049

T;T;T;T;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00060

LIST_S2

Benign

0.0060

.;T;.;.;T;.

MetaRNN

Benign

0.0032

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.78

N;N;N;N;.;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

N;N;N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.54

T;T;T;T;T;T

Sift4G

Benign

0.53

T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;B

Vest4

0.069

MPC

0.015

ClinPred

0.00078

GERP RS

-5.9

Varity_R

0.20

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over