17-29451681-G-GT

Position:

• chr17-29451681-G-GT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020791.4(TAOK1):​c.132+2dupT variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAOK1 NM_020791.4 splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.00

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Multiple lines of computational evidence support a deleterious effect 2: max_spliceai, phyloP100way_vertebrate [when was below the threshold]

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK1	NM_020791.4	c.132+2dupT		splice_region_variant, intron_variant		ENST00000261716.8	NP_065842.1
TAOK1	NM_025142.1	c.132+2dupT		splice_region_variant, intron_variant			NP_079418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAOK1	ENST00000261716.8	c.132+2dupT		splice_region_variant, intron_variant		1	NM_020791.4	ENSP00000261716.3
TAOK1	ENST00000536202.1	c.132+2dupT		splice_region_variant, intron_variant		1		ENSP00000438819.1
TAOK1	ENST00000583121.5	c.132+2dupT		splice_region_variant, intron_variant		3		ENSP00000464562.1
TAOK1	ENST00000587277.1	n.328dupT		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Goettingen

Aug 15, 2024

PM2: Variant not found in gnomAD genomes, good gnomAD genomes coverage = 30.8.Variant not found in gnomAD exomes, good gnomAD exomes coverage = 29.9.; PP3: The position is strongly conserved (phyloP = 9.99 is greater than 9.88). No other in-silico engine is available., the variant is close to the canonical splice-site, and gene has 32 reported pathogenic LOF variants. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.72		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 5
DS_DL_spliceai		0.72		Position offset: -1

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: chr17-27778699;