chr17-7845971-G-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1_ModeratePM2PP3_StrongPP5_Moderate
The NM_001348716.2(KDM6B):c.236+1G>A variant causes a splice donor change. The variant allele was found at a frequency of 0.000000684 in 1,461,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001348716.2 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDM6B | NM_001348716.2 | c.236+1G>A | splice_donor_variant | ENST00000448097.7 | |||
KDM6B | NM_001080424.2 | c.236+1G>A | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDM6B | ENST00000448097.7 | c.236+1G>A | splice_donor_variant | 5 | NM_001348716.2 | A2 | |||
KDM6B | ENST00000254846.9 | c.236+1G>A | splice_donor_variant | 1 | P2 | ||||
KDM6B | ENST00000570632.1 | c.236+1G>A | splice_donor_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461078Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726910
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | Oct 02, 2021 | Canonical splice site: predicted to alter splicing and 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 (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.