7-101173312-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198571.3(NAT16):​c.521G>A​(p.Arg174His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NAT16
NM_198571.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.372
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23941508).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAT16NM_198571.3 linkc.521G>A p.Arg174His missense_variant Exon 3 of 4 ENST00000300303.7 NP_940973.2 Q8N8M0-1
NAT16NM_001369694.1 linkc.521G>A p.Arg174His missense_variant Exon 4 of 5 NP_001356623.1
NAT16NM_001369695.1 linkc.521G>A p.Arg174His missense_variant Exon 3 of 4 NP_001356624.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAT16ENST00000300303.7 linkc.521G>A p.Arg174His missense_variant Exon 3 of 4 2 NM_198571.3 ENSP00000300303.2 Q8N8M0-1
NAT16ENST00000455377.5 linkc.521G>A p.Arg174His missense_variant Exon 4 of 5 1 ENSP00000395125.1 Q8N8M0-1
NAT16ENST00000444446.1 linkc.*52G>A downstream_gene_variant 4 ENSP00000391769.1 C9JB11

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248920
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134804
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461654
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 16, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.521G>A (p.R174H) alteration is located in exon 3 (coding exon 2) of the NAT16 gene. This alteration results from a G to A substitution at nucleotide position 521, causing the arginine (R) at amino acid position 174 to be replaced by a histidine (H). 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
0.20
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.056
T;T
Eigen
Benign
-0.035
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.78
.;T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.0
M;M
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.7
N;N
REVEL
Benign
0.14
Sift
Uncertain
0.0070
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.37
MutPred
0.31
Loss of MoRF binding (P = 0.0121);Loss of MoRF binding (P = 0.0121);
MVP
0.16
MPC
0.63
ClinPred
0.75
D
GERP RS
-0.18
Varity_R
0.11
gMVP
0.43

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: rs1254747811; hg19: chr7-100816593; API