chr6-43253604-C-T

Position:

• chr6-43253604-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032538.3(TTBK1):​c.367C>T​(p.Arg123Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTBK1 NM_032538.3 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.198

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTBK1	NM_032538.3	c.367C>T	p.Arg123Ter	stop_gained	5/15	ENST00000259750.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK1	ENST00000259750.9	c.367C>T	p.Arg123Ter	stop_gained	5/15	1	NM_032538.3	P3
TTBK1	ENST00000703836.1	c.367C>T	p.Arg123Ter	stop_gained	4/13			A2
TTBK1	ENST00000304139.6	n.376C>T		non_coding_transcript_exon_variant	4/13	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anxiety;C0004352:Autism;C0086437:Joint laxity;C0454644:Delayed speech and language development;C0856975:Autistic behavior;C4012968:Mild global developmental delay Uncertain:1

Uncertain significance, criteria provided, single submitter

research

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

May 17, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Benign	0.065
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.28	N
MutationTaster	Benign	1.0	A;A
Vest4		0.39
GERP RS		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-43221342; COSMIC: COSV52498560;