11-34113828-C-G

Variant names:

• chr11-34113828-C-G
• rs769674662
• NM_024662.3:c.485C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024662.3(NAT10):​c.485C>G​(p.Thr162Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T162I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NAT10 NM_024662.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

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.485C>G	p.Thr162Arg	missense	Exon 5 of 29	NP_078938.3	Q9H0A0-1
	NAT10	NM_001144030.2		c.269C>G	p.Thr90Arg	missense	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.485C>G	p.Thr162Arg	missense	Exon 5 of 29	ENSP00000257829.3	Q9H0A0-1
	NAT10	ENST00000891108.1		c.485C>G	p.Thr162Arg	missense	Exon 5 of 30	ENSP00000561167.1
	NAT10	ENST00000891110.1		c.485C>G	p.Thr162Arg	missense	Exon 5 of 29	ENSP00000561169.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.036	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		7.7
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.98	D
Vest4		0.86
MutPred		0.69		Gain of MoRF binding (P = 0.0037)
MVP		0.71
MPC		0.66
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.79
gMVP		0.92
Mutation Taster		=19/81	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: rs769674662; hg19: chr11-34135375;