rs1556004813
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_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
NM_016032.4 frameshift
Scores
Not classified
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
ZDHHC9 | NM_016032.4 | c.679del | p.Leu227Ter | frameshift_variant | 8/11 | ENST00000357166.11 | |
ZDHHC9 | NM_001008222.3 | c.679del | p.Leu227Ter | frameshift_variant | 7/10 | ||
ZDHHC9 | XM_047442151.1 | c.*81del | 3_prime_UTR_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZDHHC9 | ENST00000357166.11 | c.679del | p.Leu227Ter | frameshift_variant | 8/11 | 1 | NM_016032.4 | P1 | |
ZDHHC9 | ENST00000371064.7 | c.679del | p.Leu227Ter | frameshift_variant | 7/10 | 1 | P1 | ||
ZDHHC9 | ENST00000433917.5 | c.420del | p.Leu141Ter | frameshift_variant | 5/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 08, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at