17-29508120-C-T

Variant names:

• chr17-29508120-C-T
• rs508706
• NM_020791.4:c.1563C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_020791.4(TAOK1):​c.1563C>T​(p.Ala521Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 1,613,316 control chromosomes in the GnomAD database, including 583,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.86 (56453 hom., cov: 32)
  • Exomes 𝑓: 0.85 (527433 hom.)
• Consequence: TAOK1 NM_020791.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.125
• Publications: 18 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=-0.34).
• BP6: Variant 17-29508120-C-T is Benign according to our data. Variant chr17-29508120-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059233.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.125 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAOK1	NM_020791.4	c.1563C>T	p.Ala521Ala	synonymous_variant	Exon 14 of 20	ENST00000261716.8	NP_065842.1
TAOK1	NM_025142.1	c.1563C>T	p.Ala521Ala	synonymous_variant	Exon 14 of 18		NP_079418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAOK1	ENST00000261716.8	c.1563C>T	p.Ala521Ala	synonymous_variant	Exon 14 of 20	1	NM_020791.4	ENSP00000261716.3
TAOK1	ENST00000536202.1	c.1563C>T	p.Ala521Ala	synonymous_variant	Exon 14 of 18	1		ENSP00000438819.1
TAOK1	ENST00000577583.1	n.1411C>T		non_coding_transcript_exon_variant	Exon 8 of 9	2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130865 AN: 152100 Hom.: 56397 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.894

GnomAD2 exomes AF: 0.841 AC: 211269 AN: 251282 AF XY: 0.837

Gnomad AFR exome AF: 0.887

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.891

Gnomad EAS exome AF: 0.774

Gnomad FIN exome AF: 0.818

Gnomad NFE exome AF: 0.859

Gnomad OTH exome AF: 0.856

GnomAD4 exome AF: 0.849 AC: 1240337 AN: 1461098 Hom.: 527433 Cov.: 39 AF XY: 0.847 AC XY: 615724 AN XY: 726846

African (AFR) AF: 0.882 AC: 29520 AN: 33460

American (AMR) AF: 0.863 AC: 38594 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 23357 AN: 26132

East Asian (EAS) AF: 0.766 AC: 30391 AN: 39680

South Asian (SAS) AF: 0.764 AC: 65897 AN: 86216

European-Finnish (FIN) AF: 0.820 AC: 43808 AN: 53392

Middle Eastern (MID) AF: 0.894 AC: 5159 AN: 5768

European-Non Finnish (NFE) AF: 0.856 AC: 951780 AN: 1111364

Other (OTH) AF: 0.859 AC: 51831 AN: 60362

GnomAD4 genome AF: 0.860 AC: 130981 AN: 152218 Hom.: 56453 Cov.: 32 AF XY: 0.855 AC XY: 63637 AN XY: 74422

African (AFR) AF: 0.886 AC: 36808 AN: 41530

American (AMR) AF: 0.880 AC: 13451 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3069 AN: 3472

East Asian (EAS) AF: 0.771 AC: 3996 AN: 5186

South Asian (SAS) AF: 0.754 AC: 3641 AN: 4828

European-Finnish (FIN) AF: 0.808 AC: 8551 AN: 10580

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58531 AN: 68018

Other (OTH) AF: 0.891 AC: 1882 AN: 2112

Alfa AF: 0.866 Hom.: 51996

Bravo AF: 0.866

Asia WGS AF: 0.759 AC: 2637 AN: 3478

EpiCase AF: 0.876

EpiControl AF: 0.875

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TAOK1-related disorder Benign:1

Oct 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.2
DANN	Benign	0.69
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs508706; hg19: chr17-27835138; COSMIC: COSV105064567;