Genetic Variant NAT16:p.Arg250Gln (chr7-101172440-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198571.3(NAT16):c.749G>A(p.Arg250Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000282 in 1,597,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

NAT16
NM_198571.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.384

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03098312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT16	NM_198571.3 link	c.749G>A	p.Arg250Gln	missense_variant	Exon 4 of 4	ENST00000300303.7	NP_940973.2	Q8N8M0-1
NAT16	NM_001369694.1 link	c.749G>A	p.Arg250Gln	missense_variant	Exon 5 of 5		NP_001356623.1
NAT16	NM_001369695.1 link	c.749G>A	p.Arg250Gln	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.749G>A	p.Arg250Gln	missense_variant	Exon 4 of 4	2	NM_198571.3	ENSP00000300303.2		Q8N8M0-1
NAT16	ENST00000455377.5 link	c.749G>A	p.Arg250Gln	missense_variant	Exon 5 of 5	1		ENSP00000395125.1		Q8N8M0-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000922

AC:

AN:

216850

Hom.:

AF XY:

0.00000835

AC XY:

AN XY:

119782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000206

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000284

AC:

AN:

1445268

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

718680

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000316

Gnomad4 OTH exome

AF:

0.0000836

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.749G>A (p.R250Q) alteration is located in exon 4 (coding exon 3) of the NAT16 gene. This alteration results from a G to A substitution at nucleotide position 749, causing the arginine (R) at amino acid position 250 to be replaced by a glutamine (Q). 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

0.084

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0058

T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.038

Sift

Benign

0.31

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0050

B;B

Vest4

0.051

MutPred

0.27

Loss of phosphorylation at S252 (P = 0.1059);Loss of phosphorylation at S252 (P = 0.1059);

MVP

0.030

MPC

0.58

ClinPred

0.056

GERP RS

-4.8

Varity_R

0.031

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over