rs56172717

Variant names:

• chr8-18222799-A-G
• rs56172717
• NM_000662.8:c.752A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-18222799-A-G
• chr8-18222799-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000662.8(NAT1):​c.752A>G​(p.Asp251Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NAT1 NM_000662.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.752A>G	p.Asp251Gly	missense_variant	Exon 3 of 3	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.752A>G	p.Asp251Gly	missense_variant	Exon 3 of 3	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460198 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726204

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111428

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T;T;.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	.;D;.;.;D;.
M_CAP	Benign	0.0090	T
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M;M;.;M
PhyloP100		6.3
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.8	D;D;D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0050	D;D;D;D;D;D
Sift4G	Benign	0.094	T;T;T;T;D;T
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.56
MutPred		0.69		.;.;.;.;Loss of ubiquitination at K309 (P = 0.0371);.;
MVP		0.54
MPC		0.12
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.83
gMVP		0.75
Mutation Taster		=60/40	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: rs56172717; hg19: chr8-18080308;