rs1556165162
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_018486.3(HDAC8):c.104_105del(p.Pro35GlnfsTer11) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 17)
Consequence
HDAC8
NM_018486.3 frameshift
NM_018486.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.53
Genes affected
HDAC8 (HGNC:13315): (histone deacetylase 8) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant X-72572656-TGG-T is Pathogenic according to our data. Variant chrX-72572656-TGG-T is described in ClinVar as [Pathogenic]. Clinvar id is 545414.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HDAC8 | NM_018486.3 | c.104_105del | p.Pro35GlnfsTer11 | frameshift_variant | 1/11 | ENST00000373573.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HDAC8 | ENST00000373573.9 | c.104_105del | p.Pro35GlnfsTer11 | frameshift_variant | 1/11 | 1 | NM_018486.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 17
GnomAD3 genomes
?
Cov.:
17
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 17
GnomAD4 genome
?
Cov.:
17
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cornelia de Lange syndrome 5 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Medical Genetics Lab, Policlinico S. Orsola.Malpighi | May 03, 2018 | This is a predicted null variant (frameshift) in a gene (HDAC8) where loss of function is a known cause of disease. It is absent from large population databases. No other family members were affected and the variant is likely de novo in this female patient (absent in her father, sister and maternal grandomother; her mother died due to accidental causes). Mutations in HDAC8 are a known cause of Cornelia de Lange syndrome type 5 and Intellectual Disability; clinical features of this patient are consistent with those previously described in patients with HDAC8 mutations. - |
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