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GeneBe

8-18400582-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000015.3(NAT2):c.579G>T(p.Thr193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,612,926 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

NAT2
NM_000015.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.823
Variant links:
Genes affected
NAT2 (HGNC:7646): (N-acetyltransferase 2) This gene encodes an enzyme that functions to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism in which human populations segregate into rapid, intermediate, and slow acetylator phenotypes. Polymorphisms in this gene are also associated with higher incidences of cancer and drug toxicity. A second polymorphic arylamine N-acetyltransferase gene (NAT1), is located near this gene (NAT2). [provided by RefSeq, Sep 2019]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-18400582-G-T is Benign according to our data. Variant chr8-18400582-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 719326.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.823 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 142 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NAT2NM_000015.3 linkuse as main transcriptc.579G>T p.Thr193= synonymous_variant 2/2 ENST00000286479.4
NAT2XM_017012938.2 linkuse as main transcriptc.579G>T p.Thr193= synonymous_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAT2ENST00000286479.4 linkuse as main transcriptc.579G>T p.Thr193= synonymous_variant 2/21 NM_000015.3 P1
NAT2ENST00000520116.1 linkuse as main transcriptc.189G>T p.Thr63= synonymous_variant 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000934
AC:
142
AN:
152020
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00132
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.00160
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00109
AC:
272
AN:
249686
Hom.:
0
AF XY:
0.00107
AC XY:
144
AN XY:
135058
show subpopulations
Gnomad AFR exome
AF:
0.000313
Gnomad AMR exome
AF:
0.000204
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00167
Gnomad NFE exome
AF:
0.00193
Gnomad OTH exome
AF:
0.000825
GnomAD4 exome
AF:
0.00143
AC:
2087
AN:
1460788
Hom.:
1
Cov.:
47
AF XY:
0.00137
AC XY:
993
AN XY:
726648
show subpopulations
Gnomad4 AFR exome
AF:
0.000330
Gnomad4 AMR exome
AF:
0.000135
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00212
Gnomad4 NFE exome
AF:
0.00171
Gnomad4 OTH exome
AF:
0.000845
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000933
AC:
142
AN:
152138
Hom.:
0
Cov.:
31
AF XY:
0.000632
AC XY:
47
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00132
Gnomad4 NFE
AF:
0.00160
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00122
Hom.:
0
Bravo
AF:
0.000778
EpiCase
AF:
0.00104
EpiControl
AF:
0.00190

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
Cadd
Benign
0.24
Dann
Benign
0.34

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144176822; hg19: chr8-18258092; API