11-34112055-C-A

Variant names:

• chr11-34112055-C-A
• NM_024662.3:c.204C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024662.3(NAT10):​c.204C>A​(p.His68Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NAT10 NM_024662.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0790

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT10	NM_024662.3	c.204C>A	p.His68Gln	missense_variant	Exon 4 of 29	ENST00000257829.8	NP_078938.3
NAT10	NM_001144030.2	c.-13C>A		5_prime_UTR_variant	Exon 2 of 27		NP_001137502.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT10	ENST00000257829.8	c.204C>A	p.His68Gln	missense_variant	Exon 4 of 29	1	NM_024662.3	ENSP00000257829.3
NAT10	ENST00000527971.5	c.204C>A	p.His68Gln	missense_variant	Exon 3 of 8	2		ENSP00000437324.1
NAT10	ENST00000529523.5	c.204C>A	p.His68Gln	missense_variant	Exon 4 of 5	4		ENSP00000435569.1
NAT10	ENST00000531159	c.-13C>A		5_prime_UTR_variant	Exon 2 of 27	2		ENSP00000433011.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.204C>A (p.H68Q) alteration is located in exon 4 (coding exon 3) of the NAT10 gene. This alteration results from a C to A substitution at nucleotide position 204, causing the histidine (H) at amino acid position 68 to be replaced by a glutamine (Q). 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	Pathogenic	0.69
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.7	H;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-7.1	D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.91	P;.;.
Vest4		0.55
MutPred		0.45		Gain of methylation at K71 (P = 0.1053);Gain of methylation at K71 (P = 0.1053);Gain of methylation at K71 (P = 0.1053);
MVP		0.49
MPC		0.52
ClinPred		0.99	D
GERP RS		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-34133602;