8-18222506-G-C

Variant names:

• chr8-18222506-G-C
• NM_000662.8:c.459G>C
• NAT1 p.Thr153Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000662.8(NAT1):​c.459G>C​(p.Thr153Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T153T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAT1 NM_000662.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.751 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_000662.8	MANE Select	c.459G>C	p.Thr153Thr	synonymous	Exon 3 of 3	NP_000653.3
	NAT1	NM_001160175.4		c.645G>C	p.Thr215Thr	synonymous	Exon 5 of 5	NP_001153647.1	F5H5R8
	NAT1	NM_001160176.4		c.645G>C	p.Thr215Thr	synonymous	Exon 4 of 4	NP_001153648.1	F5H5R8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.459G>C	p.Thr153Thr	synonymous	Exon 3 of 3	ENSP00000307218.4	P18440
	NAT1	ENST00000518029.5	TSL:1	c.459G>C	p.Thr153Thr	synonymous	Exon 4 of 4	ENSP00000428270.1	P18440
	NAT1	ENST00000545197.3	TSL:5	c.645G>C	p.Thr215Thr	synonymous	Exon 4 of 4	ENSP00000443194.1	F5H5R8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.57
DANN	Benign	0.40
PhyloP100		-0.75

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-18080015;