chr17-29478347-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_ModeratePP5_Moderate
The NM_020791.4(TAOK1):c.449G>T(p.Arg150Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 15/25 in silico tools predict a damaging 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_020791.4 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAOK1 | NM_020791.4 | c.449G>T | p.Arg150Ile | missense_variant, splice_region_variant | 6/20 | ENST00000261716.8 | |
TAOK1 | NM_025142.1 | c.449G>T | p.Arg150Ile | missense_variant, splice_region_variant | 6/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAOK1 | ENST00000261716.8 | c.449G>T | p.Arg150Ile | missense_variant, splice_region_variant | 6/20 | 1 | NM_020791.4 | P1 | |
TAOK1 | ENST00000536202.1 | c.449G>T | p.Arg150Ile | missense_variant, splice_region_variant | 6/18 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1409948Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 699930
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 30, 2020 | The alteration results in an amino acid change:_x000D_ _x000D_ The c.449G>T (p.R150I) alteration is located in exon 6 (coding exon 5) of the TAOK1 gene. This alteration results from a G to T substitution at nucleotide position 449. This change occurs in the last base pair of coding exon 5, which makes it likely to have some effect on normal mRNA splicing. In addition to potential splicing impact, this alteration causes the arginine (R) at amino acid position 150 to be replaced by an isoleucine (I). The alteration is not observed in population databases:_x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the TAOK1 c.449G>T alteration was not observed, with coverage at this position. The altered nucleotide is conserved throughout evolution:_x000D_ _x000D_ The c.449G nucleotide is conserved in available vertebrate species. The amino acid is located in a functionally important protein domain:_x000D_ _x000D_ The p.R150 amino acid is located in the conserved kinase domain, also known as catalytic domain, of the TAOK1 protein. The catalytic domains of protein kinases contain 12 conserved subdomains that fold into a common catalytic core structure. R150 is part of the catalytic loop of subdomain VIB and adjacent to residue D151, which is likely important for the catalytic activity of that region (Hanks, 1995). The alteration is predicted deleterious by in silico modeling:_x000D_ _x000D_ The p.R150I amino acid change is predicted to be deleterious by in silico analysis. Additionally, this nucleotide change is predicted to weaken the native splice donor site based on the BDGP and ESEfinder splice site in silico tools; however, direct evidence is unavailable. Based on the available evidence, this alteration is classified as likely pathogenic. - |
DEVELOPMENTAL DELAY WITHOUT INTELLECTUAL IMPAIRMENT OR BEHAVIORAL ABNORMALITIES Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at