rs6458330

Variant names:

• chr6-43284473-G-C
• rs6458330
• NM_032538.3:c.3572+161G>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.3572+161G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,988 control chromosomes in the GnomAD database, including 8,001 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 0.30 (8001 hom., cov: 32)
• Consequence: TTBK1 NM_032538.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTBK1	NM_032538.3	c.3572+161G>C		intron_variant	Intron 14 of 14	ENST00000259750.9	NP_115927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTBK1	ENST00000259750.9	c.3572+161G>C		intron_variant	Intron 14 of 14	1	NM_032538.3	ENSP00000259750.4

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45246 AN: 151870 Hom.: 7988 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.298 AC: 45296 AN: 151988 Hom.: 8001 Cov.: 32 AF XY: 0.292 AC XY: 21686 AN XY: 74272

African (AFR) AF: 0.493 AC: 20416 AN: 41396

American (AMR) AF: 0.257 AC: 3922 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1811 AN: 5154

South Asian (SAS) AF: 0.257 AC: 1235 AN: 4812

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10598

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14768 AN: 67968

Other (OTH) AF: 0.282 AC: 597 AN: 2114

Alfa AF: 0.259 Hom.: 754

Bravo AF: 0.314

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		0.48
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: rs6458330; hg19: chr6-43252211; COSMIC: COSV107273722;