rs1222887949

Variant names:

• chr11-34108767-C-T
• rs1222887949
• NM_024662.3:c.134C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024662.3(NAT10):​c.134C>T​(p.Ser45Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAT10 NM_024662.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.134C>T	p.Ser45Phe	missense	Exon 3 of 29	NP_078938.3	Q9H0A0-1
	NAT10	NM_001144030.2		c.-17+2975C>T		intron	N/A	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.134C>T	p.Ser45Phe	missense	Exon 3 of 29	ENSP00000257829.3	Q9H0A0-1
	NAT10	ENST00000891108.1		c.134C>T	p.Ser45Phe	missense	Exon 3 of 30	ENSP00000561167.1
	NAT10	ENST00000891110.1		c.134C>T	p.Ser45Phe	missense	Exon 3 of 29	ENSP00000561169.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250676 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		7.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.038	D
Polyphen		0.14	B
Vest4		0.92
MutPred		0.52		Gain of catalytic residue at S45 (P = 0.013)
MVP		0.44
MPC		0.65
ClinPred		0.97	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.69
Mutation Taster		=15/85	disease causing

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: rs1222887949; hg19: chr11-34130314;