rs1557501

Positions:

• chrX-153931677-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA10	NM_003491.4	c.386+394G>A		intron_variant		ENST00000464845.6
NAA10	NM_001256119.2	c.341+639G>A		intron_variant
NAA10	NM_001256120.2	c.368+394G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA10	ENST00000464845.6	c.386+394G>A		intron_variant		1	NM_003491.4	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 43885 AN: 111711 Hom.: 8290 Cov.: 24 AF XY: 0.390 AC XY: 13207 AN XY: 33907

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

Gnomad4 AFR exome AF: 0.718

Gnomad4 AMR exome AF: 0.568

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.716

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.297

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

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.433

Alfa AF: 0.281 Hom.: 6406

Bravo AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1557501; hg19: chrX-153197130;