6-43245739-C-T

Position:

• chr6-43245739-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032538.3(TTBK1):​c.-54-868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,968 control chromosomes in the GnomAD database, including 18,928 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (18928 hom., cov: 31)
• Consequence: TTBK1 NM_032538.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTBK1	NM_032538.3	c.-54-868C>T		intron_variant		ENST00000259750.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK1	ENST00000259750.9	c.-54-868C>T		intron_variant		1	NM_032538.3	P3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70703 AN: 151850 Hom.: 18876 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.439

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.466 AC: 70812 AN: 151968 Hom.: 18928 Cov.: 31 AF XY: 0.462 AC XY: 34306 AN XY: 74250

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.435

Alfa AF: 0.354 Hom.: 13229

Bravo AF: 0.480

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.68

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: rs2651206; hg19: chr6-43213477;