X-153930002-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_003491.4(NAA10):c.693C>T(p.Ser231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,207,226 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 35 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000065 (0 hom. 34 hem.)
• Consequence: NAA10 NM_003491.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant X-153930002-G-A is Benign according to our data. Variant chrX-153930002-G-A is described in ClinVar as [Benign]. Clinvar id is 2988791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.62 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000271 (3/110755) while in subpopulation SAS AF= 0.000794 (2/2520). AF 95% confidence interval is 0.00014. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAA10	NM_003491.4	c.693C>T	p.Ser231=	synonymous_variant	8/8	ENST00000464845.6
NAA10	NM_001256120.2	c.675C>T	p.Ser225=	synonymous_variant	8/8
NAA10	NM_001256119.2	c.648C>T	p.Ser216=	synonymous_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAA10	ENST00000464845.6	c.693C>T	p.Ser231=	synonymous_variant	8/8	1	NM_003491.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000271 AC: 3 AN: 110755 Hom.: 0 Cov.: 22 AF XY: 0.0000303 AC XY: 1 AN XY: 32951

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.000794

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000820 AC: 15 AN: 182979 Hom.: 0 AF XY: 0.000148 AC XY: 10 AN XY: 67477

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad SAS exome AF: 0.000734

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000648 AC: 71 AN: 1096471 Hom.: 0 Cov.: 31 AF XY: 0.0000940 AC XY: 34 AN XY: 361883

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000961

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000190

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome AF: 0.0000271 AC: 3 AN: 110755 Hom.: 0 Cov.: 22 AF XY: 0.0000303 AC XY: 1 AN XY: 32951

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000281

Gnomad4 SAS AF: 0.000794

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

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

Invitae

Mar 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	0.45
Dann	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs782081670; hg19: chrX-153195455; COSMIC: COSV105252609; COSMIC: COSV105252609;