TAOK1 p.Ala521Ala

Variant names:

• chr17-29508117-T-T
• ENST00000261716.8:c.

Your query was ambiguous. Multiple possible variants found:

• chr17-29508118--
• chr17-29508120-C-T
• chr17-29508120-C-A
• chr17-29508120-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020791.4(TAOK1):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAOK1 NM_020791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• Publications: 0 publications found

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]

TAOK1 Gene-Disease associations (from GenCC):

• developmental delay with or without intellectual impairment or behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020791.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAOK1	NM_020791.4	MANE Select	c.		intron	N/A	NP_065842.1	Q7L7X3-1
	TAOK1	NM_025142.1		c.		intron	N/A	NP_079418.1	Q7L7X3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAOK1	ENST00000261716.8	TSL:1 MANE Select	c.		exon_region	Exon 14 of 20	ENSP00000261716.3	Q7L7X3-1
	TAOK1	ENST00000536202.1	TSL:1	c.		exon_region	Exon 14 of 18	ENSP00000438819.1	Q7L7X3-3
	TAOK1	ENST00000916641.1		c.		exon_region	Exon 14 of 20	ENSP00000586700.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-27835135;