Genetic Variant NAT10:p.Thr162Ile (chr11-34113828-C-T) – ACMG Classification: Uncertain_significance (4 pts)

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

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]

NAT10 links:

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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
NAT10	NM_024662.3 link	c.485C>T	p.Thr162Ile	missense_variant	Exon 5 of 29	ENST00000257829.8	NP_078938.3	Q9H0A0-1
NAT10	NM_001144030.2 link	c.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	UniProt
NAT10	ENST00000257829.8 link	c.485C>T	p.Thr162Ile	missense_variant	Exon 5 of 29	1	NM_024662.3	ENSP00000257829.3	Q9H0A0-1
NAT10	ENST00000531159.6 link	c.269C>T	p.Thr90Ile	missense_variant	Exon 3 of 27	2		ENSP00000433011.2	Q9H0A0-2
NAT10	ENST00000527971.5 link	c.485C>T	p.Thr162Ile	missense_variant	Exon 4 of 8	2		ENSP00000437324.1	E9PMU0
NAT10	ENST00000529523.5 link	c.*48C>T		downstream_gene_variant		4		ENSP00000435569.1	E9PJN6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250644

Hom.:

AF XY:

0.0000222

AC XY:

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:

AN:

1461002

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

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.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000576

AC:

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

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;.;.;.

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.044

MetaRNN

Pathogenic

0.93

D;D;D;D

MetaSVM

Uncertain

-0.041

MutationAssessor

Pathogenic

3.7

H;.;.;.

PrimateAI

Uncertain

0.78

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

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.

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