chr8-18222552-T-A

Position:

• chr8-18222552-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000662.8(NAT1):​c.505T>A​(p.Tyr169Asn) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAT1 NM_000662.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0410

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3166958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.505T>A	p.Tyr169Asn	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	c.505T>A	p.Tyr169Asn	missense_variant	3/3	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.505T>A (p.Y169N) alteration is located in exon 3 (coding exon 1) of the NAT1 gene. This alteration results from a T to A substitution at nucleotide position 505, causing the tyrosine (Y) at amino acid position 169 to be replaced by an asparagine (N). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.095	T;T;T;T;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.014	N
LIST_S2	Uncertain	0.95	.;D;.;.;D;.
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;M;M;M;.;M
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D
REVEL	Benign	0.070
Sift	Benign	0.055	T;T;T;T;D;T
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.43	B;B;B;B;P;B
Vest4		0.17
MutPred		0.75		.;.;.;.;Gain of disorder (P = 0.0241);.;
MVP		0.33
MPC		0.021
ClinPred		0.29	T
GERP RS		0.47
Varity_R		0.40
gMVP		0.55

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: chr8-18080061;