chr8-18400860-G-C

Variant names:

• chr8-18400860-G-C
• rs1799931
• NM_000015.3:c.857G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000015.3(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. 15/20 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 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 NM_000015.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000015.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT2	NM_000015.3	MANE Select	c.857G>C	p.Gly286Ala	missense	Exon 2 of 2	NP_000006.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT2	ENST00000286479.4	TSL:1 MANE Select	c.857G>C	p.Gly286Ala	missense	Exon 2 of 2	ENSP00000286479.3
	NAT2	ENST00000520116.1	TSL:3	c.467G>C	p.Gly156Ala	missense	Exon 2 of 2	ENSP00000428416.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.9
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.016
Sift	Benign	0.45	T
Sift4G	Benign	0.93	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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1799931; hg19: chr8-18258370;