Genetic Variant TAOK1:p.Ala521Ala (chr17-29508120-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.125

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.1563C>T	p.Ala521Ala	synonymous_variant	Exon 14 of 20	ENST00000261716.8	NP_065842.1	Q7L7X3-1A0A024QZ70
TAOK1	NM_025142.1 link	c.1563C>T	p.Ala521Ala	synonymous_variant	Exon 14 of 18		NP_079418.1	Q7L7X3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAOK1	ENST00000261716.8 link	c.1563C>T	p.Ala521Ala	synonymous_variant	Exon 14 of 20	1	NM_020791.4	ENSP00000261716.3	Q7L7X3-1
TAOK1	ENST00000536202.1 link	c.1563C>T	p.Ala521Ala	synonymous_variant	Exon 14 of 18	1		ENSP00000438819.1	Q7L7X3-3
TAOK1	ENST00000577583.1 link	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.:

show subpopulations

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

GnomAD3 exomes

AF:

0.841

AC:

211269

AN:

251282

Hom.:

89198

AF XY:

0.837

AC XY:

113733

AN XY:

135828

show subpopulations

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 SAS exome

AF:

0.758

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.:

AF XY:

0.847

AC XY:

615724

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.882

Gnomad4 AMR exome

AF:

0.863

Gnomad4 ASJ exome

AF:

0.894

Gnomad4 EAS exome

AF:

0.766

Gnomad4 SAS exome

AF:

0.764

Gnomad4 FIN exome

AF:

0.820

Gnomad4 NFE exome

AF:

0.856

Gnomad4 OTH exome

AF:

0.859

GnomAD4 genome

AF:

0.860

AC:

130981

AN:

152218

Hom.:

56453

Cov.:

AF XY:

0.855

AC XY:

63637

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.886

Gnomad4 AMR

AF:

0.880

Gnomad4 ASJ

AF:

0.884

Gnomad4 EAS

AF:

0.771

Gnomad4 SAS

AF:

0.754

Gnomad4 FIN

AF:

0.808

Gnomad4 NFE

AF:

0.861

Gnomad4 OTH

AF:

0.891

Alfa

AF:

0.865

Hom.:

39311

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

LINK: link

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over