17-29475765-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_020791.4(TAOK1):c.300A>G(p.Thr100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,610,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: TAOK1 NM_020791.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 17-29475765-A-G is Benign according to our data. Variant chr17-29475765-A-G is described in ClinVar as [Benign]. Clinvar id is 3056695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.108 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00211 (322/152356) while in subpopulation AFR AF= 0.00745 (310/41584). AF 95% confidence interval is 0.00677. There are 0 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 323 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAOK1	NM_020791.4	c.300A>G	p.Thr100=	synonymous_variant	4/20	ENST00000261716.8
TAOK1	NM_025142.1	c.300A>G	p.Thr100=	synonymous_variant	4/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAOK1	ENST00000261716.8	c.300A>G	p.Thr100=	synonymous_variant	4/20	1	NM_020791.4	P1
TAOK1	ENST00000536202.1	c.300A>G	p.Thr100=	synonymous_variant	4/18	1

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 323 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000543 AC: 135 AN: 248724 Hom.: 0 AF XY: 0.000417 AC XY: 56 AN XY: 134410

Gnomad AFR exome AF: 0.00741

Gnomad AMR exome AF: 0.000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000217 AC: 316 AN: 1458144 Hom.: 0 Cov.: 29 AF XY: 0.000190 AC XY: 138 AN XY: 725374

Gnomad4 AFR exome AF: 0.00699

Gnomad4 AMR exome AF: 0.000316

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.00211 AC: 322 AN: 152356 Hom.: 0 Cov.: 32 AF XY: 0.00191 AC XY: 142 AN XY: 74498

Gnomad4 AFR AF: 0.00745

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00105 Hom.: 0

Bravo AF: 0.00217

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TAOK1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 23, 2019

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	-0.54
Cadd	Benign	10
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs147203802; hg19: chr17-27802783;