X-153929940-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003491.4(NAA10):c.*47C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,100,049 control chromosomes in the GnomAD database, including 18,013 homozygotes. There are 64,991 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1727 hom., 5272 hem., cov: 22)
  • Exomes 𝑓: 0.18 (16286 hom. 59719 hem.)
• Consequence: NAA10 NM_003491.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.480

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-153929940-G-A is Benign according to our data. Variant chrX-153929940-G-A is described in ClinVar as [Benign]. Clinvar id is 1244939.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA10	NM_003491.4	c.*47C>T		3_prime_UTR_variant	8/8	ENST00000464845.6
NAA10	NM_001256119.2	c.*47C>T		3_prime_UTR_variant	7/7
NAA10	NM_001256120.2	c.*47C>T		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA10	ENST00000464845.6	c.*47C>T		3_prime_UTR_variant	8/8	1	NM_003491.4	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 17082 AN: 110399 Hom.: 1728 Cov.: 22 AF XY: 0.162 AC XY: 5271 AN XY: 32629

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00588

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.267 AC: 48096 AN: 179935 Hom.: 6639 AF XY: 0.270 AC XY: 17560 AN XY: 64943

Gnomad AFR exome AF: 0.0445

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.682

Gnomad SAS exome AF: 0.526

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.178 AC: 175675 AN: 989598 Hom.: 16286 Cov.: 19 AF XY: 0.201 AC XY: 59719 AN XY: 296498

Gnomad4 AFR exome AF: 0.0409

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.155 AC: 17078 AN: 110451 Hom.: 1727 Cov.: 22 AF XY: 0.161 AC XY: 5272 AN XY: 32691

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.212

Alfa AF: 0.129 Hom.: 2200

Bravo AF: 0.175

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.5
Dann	Benign	0.84

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: rs2071128; hg19: chrX-153195393; COSMIC: COSV63132558; COSMIC: COSV63132558;