rs56172717

chr8-18222799-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000662.8(NAT1):c.752A>T(p.Asp251Val) variant causes a missense change. The variant allele was found at a frequency of 0.00274 in 1,612,508 control chromosomes in the GnomAD database, including 11 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (10 hom.)
• Consequence: NAT1 NM_000662.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014334112).
• BS2: High AC in GnomAd at 361 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_000662.8	c.752A>T	p.Asp251Val	missense_variant	3/3	ENST00000307719.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000307719.9	c.752A>T	p.Asp251Val	missense_variant	3/3	1	NM_000662.8	P1

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 361 AN: 152194 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00335

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00241 AC: 603 AN: 249820 Hom.: 1 AF XY: 0.00246 AC XY: 332 AN XY: 135006

Gnomad AFR exome AF: 0.000494

Gnomad AMR exome AF: 0.000995

Gnomad ASJ exome AF: 0.000700

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00723

Gnomad NFE exome AF: 0.00339

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00278 AC: 4065 AN: 1460196 Hom.: 10 Cov.: 31 AF XY: 0.00274 AC XY: 1988 AN XY: 726204

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.000729

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000210

Gnomad4 FIN exome AF: 0.00714

Gnomad4 NFE exome AF: 0.00309

Gnomad4 OTH exome AF: 0.00234

GnomAD4 genome AF: 0.00237 AC: 361 AN: 152312 Hom.: 1 Cov.: 32 AF XY: 0.00248 AC XY: 185 AN XY: 74480

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.00335

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00266 Hom.: 0

Bravo AF: 0.00202

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.00241 AC: 292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.18
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;T;T;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.014	T;T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.1	M;M;M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.6	D;D;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.59
MVP		0.54
MPC		0.12
ClinPred		0.041	T
GERP RS		4.2
Varity_R		0.87
gMVP		0.77

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: rs56172717; hg19: chr8-18080308;