Variant 8-18400054-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000015.3(NAT2):c.51C>G(p.Asn17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,610,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

NAT2
NM_000015.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.186

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0739589).

BS2

High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT2	NM_000015.3 linkuse as main transcript	c.51C>G	p.Asn17Lys	missense_variant	2/2	ENST00000286479.4
NAT2	XM_017012938.2 linkuse as main transcript	c.51C>G	p.Asn17Lys	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT2	ENST00000286479.4 linkuse as main transcript	c.51C>G	p.Asn17Lys	missense_variant	2/2	1	NM_000015.3	P1
NAT2	ENST00000520116.1 linkuse as main transcript	c.-57-283C>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249186

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1458742

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725290

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.51C>G (p.N17K) alteration is located in exon 2 (coding exon 1) of the NAT2 gene. This alteration results from a C to G substitution at nucleotide position 51, causing the asparagine (N) at amino acid position 17 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

DANN

Benign

0.83

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.63

M_CAP

Benign

0.0015

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.71

D;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

REVEL

Benign

0.038

Sift

Benign

0.19

Sift4G

Benign

0.82

Polyphen

0.0020

Vest4

0.11

MutPred

0.40

Loss of stability (P = 0.0171);

MVP

0.26

MPC

0.0044

ClinPred

0.023

GERP RS

1.1

gMVP

0.21

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