Variant 8-18222237-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000662.8(NAT1):c.190C>T(p.Arg64Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00574 in 1,614,042 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts 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 0.0036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 33 hom. )

Consequence

NAT1
NM_000662.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.833

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021713734).

BP6

Variant 8-18222237-C-T is Benign according to our data. Variant chr8-18222237-C-T is described in ClinVar as [Benign]. Clinvar id is 252546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 547 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8 linkuse as main transcript	c.190C>T	p.Arg64Trp	missense_variant	3/3	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9 linkuse as main transcript	c.190C>T	p.Arg64Trp	missense_variant	3/3	1	NM_000662.8	ENSP00000307218	P1

Frequencies

GnomAD3 genomes

AF:

0.00360

AC:

547

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00685

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00335

AC:

841

AN:

251168

Hom.:

AF XY:

0.00347

AC XY:

471

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.00616

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00596

AC:

8714

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00570

AC XY:

4148

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.00213

Gnomad4 NFE exome

AF:

0.00737

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152214

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

234

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00685

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00535

Hom.:

Bravo

AF:

0.00351

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00312

AC:

379

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Dec 17, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T;T;T;.;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

-0.026

FATHMM_MKL

Benign

0.28

LIST_S2

Pathogenic

0.99

.;D;.;.;D;.

M_CAP

Benign

0.0085

MetaRNN

Benign

0.022

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

4.1

H;H;H;H;.;H

MutationTaster

Benign

0.99

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

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-7.9

D;D;D;D;D;D

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D

Vest4

0.68

MVP

0.53

MPC

0.12

ClinPred

0.10

GERP RS

1.2

Varity_R

0.92

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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