rs606231182

chrX-129829133-TAGCG-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_016032.4(ZDHHC9):c.172_175del(p.Arg58ThrfsTer26) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZDHHC9 NM_016032.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.60

Genes affected

ZDHHC9 (HGNC:18475): (zinc finger DHHC-type palmitoyltransferase 9) This gene encodes an integral membrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein forms a complex with golgin subfamily A member 7 and functions as a palmitoyltransferase. This protein specifically palmitoylates HRAS and NRAS. Mutations in this gene are associated with X-linked cognitive disability. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-129829133-TAGCG-T is Pathogenic according to our data. Variant chrX-129829133-TAGCG-T is described in ClinVar as [Pathogenic]. Clinvar id is 10709.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-129829133-TAGCG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC9	NM_016032.4	c.172_175del	p.Arg58ThrfsTer26	frameshift_variant	4/11	ENST00000357166.11
ZDHHC9	NM_001008222.3	c.172_175del	p.Arg58ThrfsTer26	frameshift_variant	3/10
ZDHHC9	XM_011531348.4	c.172_175del	p.Arg58ThrfsTer26	frameshift_variant	4/6
ZDHHC9	XM_047442151.1	c.172_175del	p.Arg58ThrfsTer26	frameshift_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC9	ENST00000357166.11	c.172_175del	p.Arg58ThrfsTer26	frameshift_variant	4/11	1	NM_016032.4	P1
ZDHHC9	ENST00000371064.7	c.172_175del	p.Arg58ThrfsTer26	frameshift_variant	3/10	1		P1
ZDHHC9	ENST00000406492.2	c.172_175del	p.Arg58ThrfsTer26	frameshift_variant	3/5	5
ZDHHC9	ENST00000433917.5	c.51_54del	p.Arg18ThrfsTer26	frameshift_variant	2/6	3

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Syndromic X-linked intellectual disability Raymond type Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

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: rs606231182; hg19: chrX-128963109;