Variant 6-43254624-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_032538.3(TTBK1):c.549C>T(p.Tyr183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,589,912 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 66 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 51 hom. )

Consequence

TTBK1
NM_032538.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 6-43254624-C-T is Benign according to our data. Variant chr6-43254624-C-T is described in ClinVar as [Benign]. Clinvar id is 783462.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 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.549C>T	p.Tyr183=	synonymous_variant	6/15	ENST00000259750.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK1	ENST00000259750.9 linkuse as main transcript	c.549C>T	p.Tyr183=	synonymous_variant	6/15	1	NM_032538.3	P3	Q5TCY1-1
TTBK1	ENST00000703836.1 linkuse as main transcript	c.549C>T	p.Tyr183=	synonymous_variant	5/13			A2
TTBK1	ENST00000304139.6 linkuse as main transcript	n.558C>T		non_coding_transcript_exon_variant	5/13	5

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2305

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0526

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00413

AC:

939

AN:

227360

Hom.:

AF XY:

0.00279

AC XY:

343

AN XY:

122788

show subpopulations

Gnomad AFR exome

AF:

0.0523

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000115

Gnomad FIN exome

AF:

0.000534

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00168

AC:

2409

AN:

1437550

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1005

AN XY:

714124

show subpopulations

Gnomad4 AFR exome

AF:

0.0562

Gnomad4 AMR exome

AF:

0.00276

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000973

Gnomad4 FIN exome

AF:

0.000398

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.0151

AC:

2307

AN:

152362

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1076

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0526

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00414

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00318

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.4

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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