17-29487478-C-T

Variant names:

• chr17-29487478-C-T
• rs559972
• NM_020791.4:c.656-2186C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020791.4(TAOK1):​c.656-2186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,748 control chromosomes in the GnomAD database, including 12,111 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (12111 hom., cov: 32)
• Consequence: TAOK1 NM_020791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 24 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, 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

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.656-2186C>T		intron	N/A	NP_065842.1
	TAOK1	NM_025142.1		c.656-2186C>T		intron	N/A	NP_079418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAOK1	ENST00000261716.8	TSL:1 MANE Select	c.656-2186C>T		intron	N/A	ENSP00000261716.3
	TAOK1	ENST00000536202.1	TSL:1	c.656-2186C>T		intron	N/A	ENSP00000438819.1
	TAOK1	ENST00000916641.1		c.656-2186C>T		intron	N/A	ENSP00000586700.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57494 AN: 151632 Hom.: 12102 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.379 AC: 57518 AN: 151748 Hom.: 12111 Cov.: 32 AF XY: 0.375 AC XY: 27818 AN XY: 74152

African (AFR) AF: 0.224 AC: 9256 AN: 41330

American (AMR) AF: 0.410 AC: 6247 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1542 AN: 3468

East Asian (EAS) AF: 0.0331 AC: 171 AN: 5172

South Asian (SAS) AF: 0.351 AC: 1686 AN: 4806

European-Finnish (FIN) AF: 0.451 AC: 4729 AN: 10482

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32442 AN: 67956

Other (OTH) AF: 0.419 AC: 880 AN: 2098

Alfa AF: 0.426 Hom.: 11596

Bravo AF: 0.369

Asia WGS AF: 0.175 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.60
PhyloP100		0.097
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs559972; hg19: chr17-27814496;