rs1555418358

Positions:

• chr15-42745910-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_173500.4(TTBK2):​c.3620A>G​(p.Glu1207Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TTBK2 NM_173500.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65

Genes affected

TTBK2 (HGNC:19141): (tau tubulin kinase 2) This gene encodes a serine-threonine kinase that putatively phosphorylates tau and tubulin proteins. Mutations in this gene cause spinocerebellar ataxia type 11 (SCA11); a neurodegenerative disease characterized by progressive ataxia and atrophy of the cerebellum and brainstem. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1743252).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTBK2	NM_173500.4	c.3620A>G	p.Glu1207Gly	missense_variant	15/15	ENST00000267890.11	NP_775771.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTBK2	ENST00000267890.11	c.3620A>G	p.Glu1207Gly	missense_variant	15/15	5	NM_173500.4	ENSP00000267890	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 08, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.0	N;.
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;.
Sift4G	Benign	0.32	T;T
Polyphen		0.92	P;.
Vest4		0.52
MutPred		0.14		Gain of MoRF binding (P = 0.0427);.;
MVP		0.093
MPC		0.94
ClinPred		0.90	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.28

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: rs1555418358; hg19: chr15-43038108;