rs1057519448

Variant names:

• chrX-153932549-A-G
• rs1057519448
• NM_003491.4:c.215T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-153932549-A-G
• chrX-153932549-A-T

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2 PP3_Strong PP5_Very_Strong

The NM_003491.4(NAA10):​c.215T>C​(p.Ile72Thr) 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 Likely pathogenic (★★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: NAA10 NM_003491.4 missense
• Clinical Significance: Likely pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 8.59

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]

ARHGAP4 (HGNC:674): (Rho GTPase activating protein 4) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this gene and a neighboring gene have been found in patients with nephrogenic diabetes insipidus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Pathogenic. Variant got 14 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.957
• PP5: Variant X-153932549-A-G is Pathogenic according to our data. Variant chrX-153932549-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 375388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153932549-A-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA10	NM_003491.4	c.215T>C	p.Ile72Thr	missense_variant	Exon 4 of 8	ENST00000464845.6	NP_003482.1
NAA10	NM_001256120.2	c.197T>C	p.Ile66Thr	missense_variant	Exon 4 of 8		NP_001243049.1
NAA10	NM_001256119.2	c.215T>C	p.Ile72Thr	missense_variant	Exon 4 of 7		NP_001243048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA10	ENST00000464845.6	c.215T>C	p.Ile72Thr	missense_variant	Exon 4 of 8	1	NM_003491.4	ENSP00000417763.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ogden syndrome Pathogenic:2

Mar 21, 2016

Baylor Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

This variant was identified in an individual with developmental delay and cardiomyopathy. -

not provided Pathogenic:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.;.;.;.;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Pathogenic	3.4	M;.;.;M;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.8	D;D;D;D;D;D
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;.;.
Polyphen		1.0	D;.;.;.;.;.
Vest4		0.87
MutPred		0.83		Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);.;.;
MVP		0.84
MPC		3.6
ClinPred		1.0	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.99
gMVP		1.0

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

LitVar

Other links and lift over

dbSNP: rs1057519448; hg19: chrX-153198002;