NM_032538.3:c.1986+4317G>C

Variant names:

• chr6-43267667-G-C
• rs1995300
• NM_032538.3:c.1986+4317G>C

Variant summary

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

The NM_032538.3(TTBK1):​c.1986+4317G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,954 control chromosomes in the GnomAD database, including 8,921 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 0.34 (8921 hom., cov: 32)
• Consequence: TTBK1 NM_032538.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTBK1	NM_032538.3	c.1986+4317G>C		intron_variant	Intron 13 of 14	ENST00000259750.9	NP_115927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTBK1	ENST00000259750.9	c.1986+4317G>C		intron_variant	Intron 13 of 14	1	NM_032538.3	ENSP00000259750.4
TTBK1	ENST00000703836.1	c.1987-1976G>C		intron_variant	Intron 12 of 12			ENSP00000515493.1
TTBK1	ENST00000304139.6	n.1996-1976G>C		intron_variant	Intron 12 of 12	5

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51950 AN: 151836 Hom.: 8915 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.342 AC: 51973 AN: 151954 Hom.: 8921 Cov.: 32 AF XY: 0.341 AC XY: 25340 AN XY: 74274

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.335

Alfa AF: 0.348 Hom.: 1143

Bravo AF: 0.337

Asia WGS AF: 0.310 AC: 1079 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	2.3
DANN	Benign	0.82

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: rs1995300; hg19: chr6-43235405;