rs6936397

chr6-43282649-G-C

Variant summary

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

The NM_032538.3(TTBK1):c.1987-78G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,257,336 control chromosomes in the GnomAD database, including 61,912 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 0.38 (12809 hom., cov: 30)
  • Exomes 𝑓: 0.29 (49103 hom.)
• Consequence: TTBK1 NM_032538.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTBK1	NM_032538.3	c.1987-78G>C		intron_variant		ENST00000259750.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK1	ENST00000259750.9	c.1987-78G>C		intron_variant		1	NM_032538.3	P3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57469 AN: 151746 Hom.: 12794 Cov.: 30

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.290 AC: 320218 AN: 1105472 Hom.: 49103 AF XY: 0.288 AC XY: 159846 AN XY: 555010

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.298

GnomAD4 genome AF: 0.379 AC: 57518 AN: 151864 Hom.: 12809 Cov.: 30 AF XY: 0.372 AC XY: 27590 AN XY: 74230

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.345

Alfa AF: 0.352 Hom.: 1357

Bravo AF: 0.390

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	6.6
Dann	Benign	0.78

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: rs6936397; hg19: chr6-43250387; COSMIC: COSV52491654;