NM_024662.3:c.459C>T

Variant names:

• chr11-34113802-C-T
• rs74471251
• NM_024662.3:c.459C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_024662.3(NAT10):​c.459C>T​(p.Thr153Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,614,024 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (50 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (56 hom.)
• Consequence: NAT10 NM_024662.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.153
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 11-34113802-C-T is Benign according to our data. Variant chr11-34113802-C-T is described in ClinVar as Benign. ClinVar VariationId is 791314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT10	NM_024662.3	MANE Select	c.459C>T	p.Thr153Thr	synonymous	Exon 5 of 29	NP_078938.3	Q9H0A0-1
	NAT10	NM_001144030.2		c.243C>T	p.Thr81Thr	synonymous	Exon 3 of 27	NP_001137502.2	Q9H0A0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT10	ENST00000257829.8	TSL:1 MANE Select	c.459C>T	p.Thr153Thr	synonymous	Exon 5 of 29	ENSP00000257829.3	Q9H0A0-1
	NAT10	ENST00000891108.1		c.459C>T	p.Thr153Thr	synonymous	Exon 5 of 30	ENSP00000561167.1
	NAT10	ENST00000891110.1		c.459C>T	p.Thr153Thr	synonymous	Exon 5 of 29	ENSP00000561169.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2548 AN: 152110 Hom.: 48 Cov.: 31

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00615

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: 0.000118

Gnomad OTH AF: 0.0149

GnomAD2 exomes AF: 0.00443 AC: 1113 AN: 251428 AF XY: 0.00330

Gnomad AFR exome AF: 0.0602

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00172 AC: 2507 AN: 1461796 Hom.: 56 Cov.: 34 AF XY: 0.00150 AC XY: 1090 AN XY: 727208

African (AFR) AF: 0.0599 AC: 2005 AN: 33476

American (AMR) AF: 0.00347 AC: 155 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.0000827 AC: 92 AN: 1111942

Other (OTH) AF: 0.00373 AC: 225 AN: 60392

GnomAD4 genome AF: 0.0169 AC: 2566 AN: 152228 Hom.: 50 Cov.: 31 AF XY: 0.0163 AC XY: 1211 AN XY: 74432

African (AFR) AF: 0.0586 AC: 2433 AN: 41516

American (AMR) AF: 0.00614 AC: 94 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68010

Other (OTH) AF: 0.0147 AC: 31 AN: 2106

Alfa AF: 0.00767 Hom.: 18

Bravo AF: 0.0191

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs74471251; hg19: chr11-34135349;