chr10-180034-C-T
Position:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001370100.5(ZMYND11):c.22C>T(p.Arg8Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 33)
Consequence
ZMYND11
NM_001370100.5 stop_gained
NM_001370100.5 stop_gained
Scores
4
2
Clinical Significance
Conservation
PhyloP100: 4.66
Genes affected
ZMYND11 (HGNC:16966): (zinc finger MYND-type containing 11) The protein encoded by this gene was first identified by its ability to bind the adenovirus E1A protein. The protein localizes to the nucleus. It functions as a transcriptional repressor, and expression of E1A inhibits this repression. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 44 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-180034-C-T is Pathogenic according to our data. Variant chr10-180034-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 393552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-180034-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZMYND11 | NM_001370100.5 | c.22C>T | p.Arg8Ter | stop_gained | 2/15 | ENST00000381604.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZMYND11 | ENST00000381604.9 | c.22C>T | p.Arg8Ter | stop_gained | 2/15 | 5 | NM_001370100.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 30 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Apr 13, 2021 | de novo variant in an individual with Seizure/epilepsy/Rx: Absence seizures, onset 8-13y, GTC onset 15y. EEG: 3-3.5Hz generalised spike and wave. Neuropsych/development: Moderate LD, macrocephaly, speech delay, enuresis; normal CT head. Dysmorphism: Hypertelorism, broad forehead, flat nasal bridge, bilateral short fifth fingers, modified palmar crease - |
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | Mar 22, 2022 | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant.It is not observed in the gnomAD v2.1.1 dataset. The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000393552). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. - |
Pathogenic, criteria provided, single submitter | research | HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology | Feb 09, 2017 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2022 | Nonsense variant predicted to result in protein truncation or nonsense-mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34216016) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 393552). This premature translational stop signal has been observed in individual(s) with clinical features of ZMYND11-related conditions (PMID: 34216016). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg8*) in the ZMYND11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZMYND11 are known to be pathogenic (PMID: 25217958). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
0.81, 0.73, 0.85, 0.82, 0.73, 0.73, 0.73, 0.85
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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