X-153930131-CG-GA

Variant names:

• chrX-153930131-CG-GA
• NM_003491.4:c.563_564delCGinsTC
• NAA10 p.Pro188Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_003491.4(NAA10):​c.563_564delCGinsTC​(p.Pro188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. P188P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: NAA10 NM_003491.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909
• Publications: 0 publications found

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]

ARHGAP4 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 26 curated pathogenic missense variants (we use a threshold of 10). The gene has 4 curated benign missense variants. Gene score misZ: 2.408 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to microphthalmia, syndromic 1, NAA10-related syndrome, Ogden syndrome, microphthalmia, Lenz type.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003491.4. 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
	NAA10	NM_003491.4	MANE Select	c.563_564delCGinsTC	p.Pro188Leu	missense	N/A	NP_003482.1	P41227-1
	NAA10	NM_001256120.2		c.545_546delCGinsTC	p.Pro182Leu	missense	N/A	NP_001243049.1
	NAA10	NM_001256119.2		c.518_519delCGinsTC	p.Pro173Leu	missense	N/A	NP_001243048.1	P41227-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAA10	ENST00000464845.6	TSL:1 MANE Select	c.563_564delCGinsTC	p.Pro188Leu	missense	N/A	ENSP00000417763.1	P41227-1
	NAA10	ENST00000370009.5	TSL:1	c.518_519delCGinsTC	p.Pro173Leu	missense	N/A	ENSP00000359026.1	P41227-2
	NAA10	ENST00000466877.5	TSL:1	n.874_875delCGinsTC		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-153195584;