chrX-153930070-T-C

Variant names:

• chrX-153930070-T-C
• NM_003491.4:c.625A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_003491.4(NAA10):​c.625A>G​(p.Ser209Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NAA10 NM_003491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

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 Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a mutagenesis_site Abolishes phosphorylation by IKKB and reduces cell growth. (size 0) in uniprot entity NAA10_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29204634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAA10	NM_003491.4	c.625A>G	p.Ser209Gly	missense_variant	Exon 8 of 8	ENST00000464845.6	NP_003482.1
NAA10	NM_001256120.2	c.607A>G	p.Ser203Gly	missense_variant	Exon 8 of 8		NP_001243049.1
NAA10	NM_001256119.2	c.580A>G	p.Ser194Gly	missense_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.625A>G	p.Ser209Gly	missense_variant	Exon 8 of 8	1	NM_003491.4	ENSP00000417763.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jul 06, 2020

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	D;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.090	N;N
REVEL	Benign	0.23
Sift	Benign	0.17	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0040	B;.
Vest4		0.28
MutPred		0.086		Loss of phosphorylation at S209 (P = 0.0075);.;
MVP		0.97
MPC		0.55
ClinPred		0.78	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.29
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153195523;