8-18400860-G-C

Position:

• chr8-18400860-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000286479.4(NAT2):​c.857G>C​(p.Gly286Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G286E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAT2 ENST00000286479.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051884383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT2	NM_000015.3	c.857G>C	p.Gly286Ala	missense_variant	2/2	ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2	c.857G>C	p.Gly286Ala	missense_variant	3/3		XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4	c.857G>C	p.Gly286Ala	missense_variant	2/2	1	NM_000015.3	ENSP00000286479	P1
NAT2	ENST00000520116.1	c.467G>C	p.Gly156Ala	missense_variant	2/2	3		ENSP00000428416

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0010
DANN	Benign	0.095
DEOGEN2	Benign	0.0074	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.10	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.016
Sift	Benign	0.45	T;T
Sift4G	Benign	0.93	T;T
Polyphen		0.0	B;.
Vest4		0.10
MutPred		0.13		Loss of methylation at K282 (P = 0.1012);.;
MVP		0.040
MPC		0.0045
ClinPred		0.10	T
GERP RS		-5.1
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-18258370;