17-29467217-G-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1_ModeratePM2PP3_StrongPP5_Moderate
The NM_020791.4(TAOK1):c.204+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,198 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 Pathogenic (★).
Frequency
Consequence
NM_020791.4 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 |
---|---|---|---|---|---|---|---|
TAOK1 | NM_020791.4 | c.204+1G>A | splice_donor_variant | ENST00000261716.8 | |||
TAOK1 | NM_025142.1 | c.204+1G>A | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAOK1 | ENST00000261716.8 | c.204+1G>A | splice_donor_variant | 1 | NM_020791.4 | P1 | |||
TAOK1 | ENST00000536202.1 | c.204+1G>A | splice_donor_variant | 1 | |||||
TAOK1 | ENST00000583121.5 | c.204+1G>A | splice_donor_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 24
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74428
ClinVar
Submissions by phenotype
TAOK1-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego | - | This variant affects the canonical splice donor site of intron 3 and is therefore predicted to interfere with splicing and result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has not been previously reported or functionally characterized in the literature to our knowledge. The TAOK1 gene is highly constrained (Z-score=4.82 and pLI=1), which suggests it is intolerant to variation. The c.204+1G>A variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.0004% (1/248798) and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.204+1G>A variant is classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at