rs1556004813

Positions:

• chrX-129812815-AG-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_016032.4(ZDHHC9):​c.679del​(p.Leu227Ter) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZDHHC9 NM_016032.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.63

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 12 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-129812815-AG-A is Pathogenic according to our data. Variant chrX-129812815-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 521595.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC9	NM_016032.4	c.679del	p.Leu227Ter	frameshift_variant	8/11	ENST00000357166.11	NP_057116.2
ZDHHC9	NM_001008222.3	c.679del	p.Leu227Ter	frameshift_variant	7/10		NP_001008223.1
ZDHHC9	XM_047442151.1	c.*81del		3_prime_UTR_variant	8/8		XP_047298107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC9	ENST00000357166.11	c.679del	p.Leu227Ter	frameshift_variant	8/11	1	NM_016032.4	ENSP00000349689	P1
ZDHHC9	ENST00000371064.7	c.679del	p.Leu227Ter	frameshift_variant	7/10	1		ENSP00000360103	P1
ZDHHC9	ENST00000433917.5	c.420del	p.Leu141Ter	frameshift_variant	5/6	3		ENSP00000406165

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 08, 2017

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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: rs1556004813; hg19: chrX-128946791;