8-18222492-G-A

Position:

chr8-18222492-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000662.8(NAT1):c.445G>A(p.Val149Ile) 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 1,614,078 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. Variant has been reported in ClinVar as Benign (★★). 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

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 1.39

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013121098).

BP6

Variant 8-18222492-G-A is Benign according to our data. Variant chr8-18222492-G-A is described in ClinVar as [Benign]. Clinvar id is 17808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-18222492-G-A is described in Lovd as [Benign].

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.445G>A	p.Val149Ile	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.445G>A	p.Val149Ile	missense_variant	3/3	1	NM_000662.8	P1

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2751

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00636

Gnomad SAS

AF:

0.0357

Gnomad FIN

AF:

0.00886

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0203

AC:

5103

AN:

251186

Hom.:

AF XY:

0.0217

AC XY:

2941

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0427

Gnomad EAS exome

AF:

0.00778

Gnomad SAS exome

AF:

0.0276

Gnomad FIN exome

AF:

0.00864

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0289

GnomAD4 exome

AF:

0.0218

AC:

31878

AN:

1461838

Hom.:

434

Cov.:

AF XY:

0.0224

AC XY:

16269

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.0115

Gnomad4 ASJ exome

AF:

0.0446

Gnomad4 EAS exome

AF:

0.00582

Gnomad4 SAS exome

AF:

0.0270

Gnomad4 FIN exome

AF:

0.00957

Gnomad4 NFE exome

AF:

0.0224

Gnomad4 OTH exome

AF:

0.0269

GnomAD4 genome

AF:

0.0181

AC:

2759

AN:

152240

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1293

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00498

Gnomad4 AMR

AF:

0.0147

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.00637

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.00886

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0240

Hom.:

109

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:

2536

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

NAT1*17 ALLELE

Other:1

other, no assertion criteria provided

literature only

OMIM

Apr 20, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.78

DANN

Benign

0.17

DEOGEN2

Benign

0.028

T;T;T;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.51

.;T;.;.;T;.

MetaRNN

Benign

0.013

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.6

N;N;N;N;.;N

MutationTaster

Benign

4.5e-12

A;A;A;A;A;A;A;A

PrimateAI

Benign

0.37

PROVEAN

Benign

0.12

N;N;N;N;N;N

REVEL

Benign

0.024

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;B

Vest4

0.021

MPC

0.015

ClinPred

0.00042

GERP RS

0.34

Varity_R

0.035

gMVP

0.30

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over