rs5030839

Positions:

• chr8-18222606-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000662.8(NAT1):​c.559C>T​(p.Arg187Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,612,750 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (15 hom.)
• Consequence: NAT1 NM_000662.8 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 335 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.559C>T	p.Arg187Ter	stop_gained	3/3	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.559C>T	p.Arg187Ter	stop_gained	3/3	1	NM_000662.8	ENSP00000307218	P1

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 335 AN: 152114 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00241 AC: 602 AN: 249942 Hom.: 3 AF XY: 0.00235 AC XY: 318 AN XY: 135084

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00291

Gnomad ASJ exome AF: 0.00251

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000461

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00356

Gnomad OTH exome AF: 0.00545

GnomAD4 exome AF: 0.00228 AC: 3329 AN: 1460518 Hom.: 15 Cov.: 32 AF XY: 0.00232 AC XY: 1687 AN XY: 726506

Gnomad4 AFR exome AF: 0.00210

Gnomad4 AMR exome AF: 0.00321

Gnomad4 ASJ exome AF: 0.00234

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000430

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00248

Gnomad4 OTH exome AF: 0.00327

GnomAD4 genome AF: 0.00220 AC: 335 AN: 152232 Hom.: 2 Cov.: 32 AF XY: 0.00204 AC XY: 152 AN XY: 74440

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00299

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00289 Hom.: 2

Bravo AF: 0.00274

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00314 AC: 27

ExAC AF: 0.00268 AC: 326

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00425

EpiControl AF: 0.00510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0031	T
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	36
DANN	Benign	0.96
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.032	N
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
Vest4		0.83
GERP RS		-0.58

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

Other links and lift over

dbSNP: rs5030839; hg19: chr8-18080115;