dbSNP rs4986783: NAT1:p.Ser214Pro (chr8-18222687-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000662.8(NAT1):c.640T>C(p.Ser214Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0750

Publications

0 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11055559).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NAT1	NM_000662.8	MANE Select	c.640T>C	p.Ser214Pro	missense	Exon 3 of 3	NP_000653.3
NAT1	NM_001160175.4		c.826T>C	p.Ser276Pro	missense	Exon 5 of 5	NP_001153647.1
NAT1	NM_001160176.4		c.826T>C	p.Ser276Pro	missense	Exon 4 of 4	NP_001153648.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NAT1	ENST00000307719.9	TSL:1 MANE Select	c.640T>C	p.Ser214Pro	missense	Exon 3 of 3	ENSP00000307218.4
NAT1	ENST00000518029.5	TSL:1	c.640T>C	p.Ser214Pro	missense	Exon 4 of 4	ENSP00000428270.1
NAT1	ENST00000545197.3	TSL:5	c.826T>C	p.Ser276Pro	missense	Exon 4 of 4	ENSP00000443194.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111958

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.098

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.47

M_CAP

Benign

0.0030

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

-0.075

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.3

REVEL

Benign

0.015

Sift

Benign

0.072

Sift4G

Benign

0.14

Polyphen

0.17

Vest4

0.098

MutPred

0.45

Gain of relative solvent accessibility (P = 0.0166)

MVP

0.10

MPC

0.015

ClinPred

0.11

GERP RS

-5.9

Varity_R

0.66

gMVP

0.57

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over