Genetic Variant NAT16:p.Asp222Glu (chr7-101172523-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198571.3(NAT16):c.666C>G(p.Asp222Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

NAT16
NM_198571.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.377

Publications

0 publications found

Variant links:

Genes affected

NAT16 (HGNC:22030): (N-acetyltransferase 16 (putative)) Predicted to enable acyltransferase activity, transferring groups other than amino-acyl groups. [provided by Alliance of Genome Resources, Apr 2022]

NAT16 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041201413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT16	NM_198571.3 link	c.666C>G	p.Asp222Glu	missense_variant	Exon 4 of 4	ENST00000300303.7	NP_940973.2	Q8N8M0-1
NAT16	NM_001369694.1 link	c.666C>G	p.Asp222Glu	missense_variant	Exon 5 of 5		NP_001356623.1
NAT16	NM_001369695.1 link	c.666C>G	p.Asp222Glu	missense_variant	Exon 4 of 4		NP_001356624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT16	ENST00000300303.7 link	c.666C>G	p.Asp222Glu	missense_variant	Exon 4 of 4	2	NM_198571.3	ENSP00000300303.2		Q8N8M0-1
NAT16	ENST00000455377.5 link	c.666C>G	p.Asp222Glu	missense_variant	Exon 5 of 5	1		ENSP00000395125.1		Q8N8M0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 12, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.666C>G (p.D222E) alteration is located in exon 4 (coding exon 3) of the NAT16 gene. This alteration results from a C to G substitution at nucleotide position 666, causing the aspartic acid (D) at amino acid position 222 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.0031

T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.34

.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

PhyloP100

0.38

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.051

Sift

Benign

1.0

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.34

B;B

Vest4

0.017

MutPred

0.20

Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);

MVP

0.030

MPC

0.46

ClinPred

0.12

GERP RS

2.4

Varity_R

0.070

gMVP

0.23

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over