chr7-101172440-C-T

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

1
18

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]

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
NAT16NM_198571.3 linkc.749G>A p.Arg250Gln missense_variant Exon 4 of 4 ENST00000300303.7 NP_940973.2 Q8N8M0-1
NAT16NM_001369694.1 linkc.749G>A p.Arg250Gln missense_variant Exon 5 of 5 NP_001356623.1
NAT16NM_001369695.1 linkc.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
NAT16ENST00000300303.7 linkc.749G>A p.Arg250Gln missense_variant Exon 4 of 4 2 NM_198571.3 ENSP00000300303.2 Q8N8M0-1
NAT16ENST00000455377.5 linkc.749G>A p.Arg250Gln missense_variant Exon 5 of 5 1 ENSP00000395125.1 Q8N8M0-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152168
Hom.:
0
Cov.:
32
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:
2
AN:
216850
Hom.:
0
AF XY:
0.00000835
AC XY:
1
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:
41
AN:
1445268
Hom.:
0
Cov.:
33
AF XY:
0.0000292
AC XY:
21
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:
4
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
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
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0058
T;T
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.78
.;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.031
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.76
N;N
PrimateAI
Benign
0.36
T
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
T
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.

Other links and lift over

dbSNP: rs551457672; hg19: chr7-100815721; API