17-29451563-CAG-C

Position:

• chr17-29451563-CAG-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The ENST00000261716.8(TAOK1):​c.18_19del​(p.Arg6SerfsTer8) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAOK1 ENST00000261716.8 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.99

Genes affected

TAOK1 (HGNC:29259): (TAO kinase 1) Enables alpha-tubulin binding activity; beta-tubulin binding activity; and kinase activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; negative regulation of microtubule depolymerization; and positive regulation of JNK cascade. Located in microtubule cytoskeleton and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 12 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 45 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-29451563-CAG-C is Pathogenic according to our data. Variant chr17-29451563-CAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 1712256.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK1	NM_020791.4	c.18_19del	p.Arg6SerfsTer8	frameshift_variant	2/20	ENST00000261716.8	NP_065842.1
TAOK1	NM_025142.1	c.18_19del	p.Arg6SerfsTer8	frameshift_variant	2/18		NP_079418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAOK1	ENST00000261716.8	c.18_19del	p.Arg6SerfsTer8	frameshift_variant	2/20	1	NM_020791.4	ENSP00000261716	P1
TAOK1	ENST00000536202.1	c.18_19del	p.Arg6SerfsTer8	frameshift_variant	2/18	1		ENSP00000438819
TAOK1	ENST00000583121.5	c.18_19del	p.Arg6SerfsTer8	frameshift_variant	3/5	3		ENSP00000464562
TAOK1	ENST00000587277.1	n.212_213del		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental delay with or without intellectual impairment or behavioral abnormalities Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen

Oct 26, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-27778581;