Variant chr6-80007993-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_003318.5(TTK):c.324T>A(p.Ser108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TTK
NM_003318.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

TTK (HGNC:12401): (TTK protein kinase) This gene encodes a dual specificity protein kinase with the ability to phosphorylate tyrosine, serine and threonine. Associated with cell proliferation, this protein is essential for chromosome alignment at the centromere during mitosis and is required for centrosome duplication. It has been found to be a critical mitotic checkpoint protein for accurate segregation of chromosomes during mitosis. Tumorigenesis may occur when this protein fails to degrade and produces excess centrosomes resulting in aberrant mitotic spindles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

TTK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTK	NM_003318.5 linkuse as main transcript	c.324T>A	p.Ser108Arg	missense_variant	3/22	ENST00000369798.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTK	ENST00000369798.7 linkuse as main transcript	c.324T>A	p.Ser108Arg	missense_variant	3/22	1	NM_003318.5	P4	P33981-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150568

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0112

AC:

11652

AN:

1038648

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

5425

AN XY:

532258

show subpopulations

Gnomad4 AFR exome

AF:

0.00555

Gnomad4 AMR exome

AF:

0.000277

Gnomad4 ASJ exome

AF:

0.00266

Gnomad4 EAS exome

AF:

0.00129

Gnomad4 SAS exome

AF:

0.00415

Gnomad4 FIN exome

AF:

0.000118

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.00750

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

150568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73478

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.324T>A (p.S108R) alteration is located in exon 3 (coding exon 2) of the TTK gene. This alteration results from a T to A substitution at nucleotide position 324, causing the serine (S) at amino acid position 108 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.89

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.45

T;T;T;T;T;T

MetaSVM

Uncertain

0.44

MutationAssessor

Uncertain

2.6

M;M;M;.;.;.

MutationTaster

Benign

0.94

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.0

N;N;N;D;D;D

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D;D;D

Polyphen

1.0

.;.;D;.;.;.

Vest4

0.61

MutPred

0.23

Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);Gain of MoRF binding (P = 0.0286);

MVP

0.83

MPC

0.57

ClinPred

0.98

GERP RS

4.5

Varity_R

0.87

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over