11-34113828-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024662.3(NAT10):​c.485C>T​(p.Thr162Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NAT10
NM_024662.3 missense

Scores

9
8
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71
Variant links:
Genes affected
NAT10 (HGNC:29830): (N-acetyltransferase 10) The protein encoded by this gene is an RNA cytidine acetyltransferase involved in histone acetylation, tRNA acetylation, the biosynthesis of 18S rRNA, and the enhancement of nuclear architecture and chromatin organization. [provided by RefSeq, Oct 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAT10NM_024662.3 linkc.485C>T p.Thr162Ile missense_variant Exon 5 of 29 ENST00000257829.8 NP_078938.3 Q9H0A0-1
NAT10NM_001144030.2 linkc.269C>T p.Thr90Ile missense_variant Exon 3 of 27 NP_001137502.2 Q9H0A0-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAT10ENST00000257829.8 linkc.485C>T p.Thr162Ile missense_variant Exon 5 of 29 1 NM_024662.3 ENSP00000257829.3 Q9H0A0-1
NAT10ENST00000531159.6 linkc.269C>T p.Thr90Ile missense_variant Exon 3 of 27 2 ENSP00000433011.2 Q9H0A0-2
NAT10ENST00000527971.5 linkc.485C>T p.Thr162Ile missense_variant Exon 4 of 8 2 ENSP00000437324.1 E9PMU0
NAT10ENST00000529523.5 linkc.*48C>T downstream_gene_variant 4 ENSP00000435569.1 E9PJN6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250644
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135434
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000175
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:
0.00000616
AC:
9
AN:
1461002
Hom.:
0
Cov.:
34
AF XY:
0.00000688
AC XY:
5
AN XY:
726764
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000135
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756
ExAC
AF:
0.0000576
AC:
7

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.485C>T (p.T162I) alteration is located in exon 5 (coding exon 4) of the NAT10 gene. This alteration results from a C to T substitution at nucleotide position 485, causing the threonine (T) at amino acid position 162 to be replaced by an isoleucine (I). 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
Uncertain
0.49
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
T;.;.;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D;D;D
M_CAP
Benign
0.044
D
MetaRNN
Pathogenic
0.93
D;D;D;D
MetaSVM
Uncertain
-0.041
T
MutationAssessor
Pathogenic
3.7
H;.;.;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-5.8
D;D;D;.
REVEL
Uncertain
0.60
Sift
Pathogenic
0.0
D;D;D;.
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
0.96
D;.;.;.
Vest4
0.88
MutPred
0.75
Gain of ubiquitination at K158 (P = 0.0666);.;Gain of ubiquitination at K158 (P = 0.0666);.;
MVP
0.74
MPC
0.68
ClinPred
1.0
D
GERP RS
5.9
Varity_R
0.76
gMVP
0.87

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: rs769674662; hg19: chr11-34135375; API