chr8-18400701-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000015.3(NAT2):c.698G>C(p.Cys233Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
NAT2
NM_000015.3 missense
NM_000015.3 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 3.34
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 GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAT2 | NM_000015.3 | c.698G>C | p.Cys233Ser | missense_variant | 2/2 | ENST00000286479.4 | |
NAT2 | XM_017012938.2 | c.698G>C | p.Cys233Ser | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAT2 | ENST00000286479.4 | c.698G>C | p.Cys233Ser | missense_variant | 2/2 | 1 | NM_000015.3 | P1 | |
NAT2 | ENST00000520116.1 | c.308G>C | p.Cys103Ser | missense_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152076Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250710Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135550
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461632Hom.: 0 Cov.: 39 AF XY: 0.00000275 AC XY: 2AN XY: 727128
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74274
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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 | Feb 17, 2022 | The c.698G>C (p.C233S) alteration is located in exon 2 (coding exon 1) of the NAT2 gene. This alteration results from a G to C substitution at nucleotide position 698, causing the cysteine (C) at amino acid position 233 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Loss of catalytic residue at C233 (P = 0.0741);.;
MVP
MPC
ClinPred
T
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