X-153931677-C-T

Variant names:

• chrX-153931677-C-T
• rs1557501
• NM_003491.4:c.386+394G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003491.4(NAA10):​c.386+394G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 885,635 control chromosomes in the GnomAD database, including 26,364 homozygotes. There are 65,388 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (8296 hom., 13255 hem., cov: 24)
  • Exomes 𝑓: 0.22 (18068 hom. 52133 hem.)
• Consequence: NAA10 NM_003491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

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.386+394G>A		intron	N/A	NP_003482.1	P41227-1
	NAA10	NM_001256120.2		c.368+394G>A		intron	N/A	NP_001243049.1
	NAA10	NM_001256119.2		c.341+639G>A		intron	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.386+394G>A		intron	N/A	ENSP00000417763.1	P41227-1
	NAA10	ENST00000370009.5	TSL:1	c.341+639G>A		intron	N/A	ENSP00000359026.1	P41227-2
	NAA10	ENST00000466877.5	TSL:1	n.697+394G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.393 AC: 43885 AN: 111711 Hom.: 8290 Cov.: 24

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.0364

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.224 AC: 173051 AN: 773871 Hom.: 18068 Cov.: 30 AF XY: 0.228 AC XY: 52133 AN XY: 228605

African (AFR) AF: 0.718 AC: 12312 AN: 17136

American (AMR) AF: 0.568 AC: 4324 AN: 7615

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 2230 AN: 7619

East Asian (EAS) AF: 0.716 AC: 7055 AN: 9849

South Asian (SAS) AF: 0.561 AC: 15025 AN: 26779

European-Finnish (FIN) AF: 0.178 AC: 1221 AN: 6872

Middle Eastern (MID) AF: 0.385 AC: 623 AN: 1618

European-Non Finnish (NFE) AF: 0.182 AC: 121730 AN: 667642

Other (OTH) AF: 0.297 AC: 8531 AN: 28741

GnomAD4 genome AF: 0.393 AC: 43942 AN: 111764 Hom.: 8296 Cov.: 24 AF XY: 0.390 AC XY: 13255 AN XY: 33970

African (AFR) AF: 0.703 AC: 21539 AN: 30648

American (AMR) AF: 0.504 AC: 5358 AN: 10621

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 711 AN: 2652

East Asian (EAS) AF: 0.712 AC: 2501 AN: 3515

South Asian (SAS) AF: 0.578 AC: 1571 AN: 2716

European-Finnish (FIN) AF: 0.193 AC: 1176 AN: 6103

Middle Eastern (MID) AF: 0.376 AC: 82 AN: 218

European-Non Finnish (NFE) AF: 0.194 AC: 10321 AN: 53084

Other (OTH) AF: 0.433 AC: 658 AN: 1521

Alfa AF: 0.309 Hom.: 10832

Bravo AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.56
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1557501; hg19: chrX-153197130;