rs398122969
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000611820.5(KDM6A):c.2065_2068del(p.Ser689ThrfsTer53) 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). Synonymous variant affecting the same amino acid position (i.e. L688L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
KDM6A
ENST00000611820.5 frameshift
ENST00000611820.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.31
Genes affected
KDM6A (HGNC:12637): (lysine demethylase 6A) This gene is located on the X chromosome and is the corresponding locus to a Y-linked gene which encodes a tetratricopeptide repeat (TPR) protein. The encoded protein of this gene contains a JmjC-domain and catalyzes the demethylation of tri/dimethylated histone H3. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
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-45063799-ACTAT-A is Pathogenic according to our data. Variant chrX-45063799-ACTAT-A is described in ClinVar as [Pathogenic]. Clinvar id is 91403.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-45063799-ACTAT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KDM6A | NM_001291415.2 | c.2065_2068del | p.Ser689ThrfsTer53 | frameshift_variant | 17/30 | ENST00000611820.5 | NP_001278344.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KDM6A | ENST00000611820.5 | c.2065_2068del | p.Ser689ThrfsTer53 | frameshift_variant | 17/30 | 1 | NM_001291415.2 | ENSP00000483595 | P4 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Kabuki syndrome 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2013 | - - |
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