Variant rs3800294 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032538.3(TTBK1):c.1868G>C(p.Gly623Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,569,006 control chromosomes in the GnomAD database, including 91,154 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9030 hom., cov: 33)

Exomes 𝑓: 0.34 ( 82124 hom. )

Consequence

TTBK1
NM_032538.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

TTBK1 (HGNC:19140): (tau tubulin kinase 1) Summary:This gene belongs to the casein kinase 1 superfamily. The encoded protein is a neuron-specific, serine/threonine and tyrosine kinase, which regulates phosphorylation of tau, a protein that associates with microtubule assemblies and stabilizes them. Genetic variants in this gene are associated with Alzheimer's disease. [provided by RefSeq, Jul 2016]

TTBK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034447312).

BP6

Variant 6-43263232-G-C is Benign according to our data. Variant chr6-43263232-G-C is described in ClinVar as [Benign]. Clinvar id is 1341645.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTBK1	NM_032538.3 linkuse as main transcript	c.1868G>C	p.Gly623Ala	missense_variant	13/15	ENST00000259750.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK1	ENST00000259750.9 linkuse as main transcript	c.1868G>C	p.Gly623Ala	missense_variant	13/15	1	NM_032538.3	P3	Q5TCY1-1
TTBK1	ENST00000703836.1 linkuse as main transcript	c.1868G>C	p.Gly623Ala	missense_variant	12/13			A2
TTBK1	ENST00000304139.6 linkuse as main transcript	n.1877G>C		non_coding_transcript_exon_variant	12/13	5

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52291

AN:

152014

Hom.:

9024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.340

GnomAD3 exomes

AF:

0.320

AC:

57073

AN:

178416

Hom.:

9161

AF XY:

0.322

AC XY:

30901

AN XY:

96114

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.290

Gnomad EAS exome

AF:

0.335

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.357

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.340

AC:

481633

AN:

1416874

Hom.:

82124

Cov.:

AF XY:

0.340

AC XY:

238006

AN XY:

700430

show subpopulations

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.344

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.343

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.344

AC:

52316

AN:

152132

Hom.:

9030

Cov.:

AF XY:

0.343

AC XY:

25536

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.362

Gnomad4 NFE

AF:

0.343

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.287

Hom.:

1796

Bravo

AF:

0.339

TwinsUK

AF:

0.334

AC:

1239

ALSPAC

AF:

0.343

AC:

1322

ESP6500AA

AF:

0.312

AC:

1348

ESP6500EA

AF:

0.317

AC:

2693

ExAC

AF:

0.271

AC:

31196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.0068

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.099

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.61

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.016

MPC

0.34

ClinPred

0.00058

GERP RS

3.8

Varity_R

0.050

gMVP

0.18

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