rs6936397

Variant names:

• chr6-43282649-G-C
• rs6936397
• NM_032538.3:c.1987-78G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032538.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTBK1	NM_032538.3	MANE Select	c.1987-78G>C		intron	N/A	NP_115927.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTBK1	ENST00000259750.9	TSL:1 MANE Select	c.1987-78G>C		intron	N/A	ENSP00000259750.4

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

African (AFR) AF: 0.644 AC: 16106 AN: 25004

American (AMR) AF: 0.226 AC: 6902 AN: 30504

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 3826 AN: 18588

East Asian (EAS) AF: 0.235 AC: 8868 AN: 37740

South Asian (SAS) AF: 0.261 AC: 17491 AN: 67004

European-Finnish (FIN) AF: 0.259 AC: 12659 AN: 48938

Middle Eastern (MID) AF: 0.252 AC: 1212 AN: 4802

European-Non Finnish (NFE) AF: 0.290 AC: 238920 AN: 825204

Other (OTH) AF: 0.298 AC: 14234 AN: 47688

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

African (AFR) AF: 0.631 AC: 26095 AN: 41370

American (AMR) AF: 0.293 AC: 4472 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1366 AN: 5148

South Asian (SAS) AF: 0.270 AC: 1297 AN: 4804

European-Finnish (FIN) AF: 0.261 AC: 2768 AN: 10586

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19818 AN: 67910

Other (OTH) AF: 0.345 AC: 725 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.78
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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