rs2071128

Variant names:

• chrX-153929940-G-A
• rs2071128
• ENST00000466877.5:n.1066C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-153929940-G-A
• chrX-153929940-G-C
• chrX-153929940-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000466877.5(NAA10):​n.1066C>T variant causes a non coding transcript exon 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 ENST00000466877.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.480
• Publications: 16 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 -20 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 VariationId is 1244939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
NAA10	NM_003491.4	c.*47C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000464845.6	NP_003482.1
NAA10	NM_001256120.2	c.*47C>T		3_prime_UTR_variant	Exon 8 of 8		NP_001243049.1
NAA10	NM_001256119.2	c.*47C>T		3_prime_UTR_variant	Exon 7 of 7		NP_001243048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAA10	ENST00000464845.6	c.*47C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_003491.4	ENSP00000417763.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 17082 AN: 110399 Hom.: 1728 Cov.: 22

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

GnomAD2 exomes AF: 0.267 AC: 48096 AN: 179935 AF XY: 0.270

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 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

African (AFR) AF: 0.0409 AC: 991 AN: 24257

American (AMR) AF: 0.477 AC: 16650 AN: 34893

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 4965 AN: 18639

East Asian (EAS) AF: 0.661 AC: 19663 AN: 29732

South Asian (SAS) AF: 0.519 AC: 27004 AN: 52035

European-Finnish (FIN) AF: 0.113 AC: 4484 AN: 39798

Middle Eastern (MID) AF: 0.338 AC: 1322 AN: 3912

European-Non Finnish (NFE) AF: 0.123 AC: 91385 AN: 743808

Other (OTH) AF: 0.217 AC: 9211 AN: 42524

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

African (AFR) AF: 0.0437 AC: 1334 AN: 30523

American (AMR) AF: 0.359 AC: 3710 AN: 10343

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 620 AN: 2617

East Asian (EAS) AF: 0.668 AC: 2294 AN: 3436

South Asian (SAS) AF: 0.517 AC: 1287 AN: 2490

European-Finnish (FIN) AF: 0.101 AC: 599 AN: 5927

Middle Eastern (MID) AF: 0.288 AC: 62 AN: 215

European-Non Finnish (NFE) AF: 0.130 AC: 6846 AN: 52701

Other (OTH) AF: 0.212 AC: 322 AN: 1519

Alfa AF: 0.130 Hom.: 2460

Bravo AF: 0.175

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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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
PhyloP100		0.48
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: rs2071128; hg19: chrX-153195393; COSMIC: COSV63132558; COSMIC: COSV63132558;