chrX-153933994-T-G

Position:

• chrX-153933994-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_003491.4(NAA10):​c.128A>C​(p.Tyr43Ser) 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NAA10 NM_003491.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.46

Genes affected

NAA10 (HGNC:18704): (N-alpha-acetyltransferase 10, NatA catalytic subunit) N-alpha-acetylation is among the most common post-translational protein modifications in eukaryotic cells. This process involves the transfer of an acetyl group from acetyl-coenzyme A to the alpha-amino group on a nascent polypeptide and is essential for normal cell function. This gene encodes an N-terminal acetyltransferase that functions as the catalytic subunit of the major amino-terminal acetyltransferase A complex. Mutations in this gene are the cause of Ogden syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

NAA10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.907
• PP5: Variant X-153933994-T-G is Pathogenic according to our data. Variant chrX-153933994-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 218104.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-153933994-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAA10	NM_003491.4	c.128A>C	p.Tyr43Ser	missense_variant	3/8	ENST00000464845.6	NP_003482.1
NAA10	NM_001256120.2	c.128A>C	p.Tyr43Ser	missense_variant	3/8		NP_001243049.1
NAA10	NM_001256119.2	c.128A>C	p.Tyr43Ser	missense_variant	3/7		NP_001243048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAA10	ENST00000464845.6	c.128A>C	p.Tyr43Ser	missense_variant	3/8	1	NM_003491.4	ENSP00000417763.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ogden syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 02, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	32
DANN	Benign	0.97
DEOGEN2	Uncertain	0.54	D;.;.;.;.;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D
M_CAP	Pathogenic	0.56	D
MetaRNN	Pathogenic	0.91	D;D;D;D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.7	M;.;.;M;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.8	D;D;D;D;D;D
REVEL	Uncertain	0.59
Sift	Benign	0.053	T;T;D;T;D;D
Sift4G	Uncertain	0.050	T;T;T;D;.;.
Polyphen		0.78	P;.;.;.;.;.
Vest4		0.81
MutPred		0.72		Gain of disorder (P = 0.0047);Gain of disorder (P = 0.0047);Gain of disorder (P = 0.0047);Gain of disorder (P = 0.0047);Gain of disorder (P = 0.0047);Gain of disorder (P = 0.0047);
MVP		0.90
MPC		2.5
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -33

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs863225427; hg19: chrX-153199447;