8-18400458-T-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000015.3(NAT2):āc.455T>Gā(p.Leu152Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,613,596 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 30)
Exomes š: 0.000034 ( 0 hom. )
Consequence
NAT2
NM_000015.3 missense
NM_000015.3 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 6.53
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151864Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250886Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135604
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461732Hom.: 0 Cov.: 57 AF XY: 0.0000289 AC XY: 21AN XY: 727168
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 151864Hom.: 0 Cov.: 30 AF XY: 0.0000270 AC XY: 2AN XY: 74160
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2024 | The c.455T>G (p.L152W) alteration is located in exon 2 (coding exon 1) of the NAT2 gene. This alteration results from a T to G substitution at nucleotide position 455, causing the leucine (L) at amino acid position 152 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at