15-42745117-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173500.4(TTBK2):c.*678A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 152,576 control chromosomes in the GnomAD database, including 163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (162 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (1 hom.)
• Consequence: TTBK2 NM_173500.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-42745117-T-C is Benign according to our data. Variant chr15-42745117-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 315967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTBK2	NM_173500.4	c.*678A>G		3_prime_UTR_variant	15/15	ENST00000267890.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK2	ENST00000267890.11	c.*678A>G		3_prime_UTR_variant	15/15	5	NM_173500.4	P1

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3727 AN: 150260 Hom.: 161 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00823

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.0161

GnomAD4 exome AF: 0.00499 AC: 11 AN: 2206 Hom.: 1 Cov.: 0 AF XY: 0.00455 AC XY: 5 AN XY: 1098

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0215

GnomAD4 genome AF: 0.0249 AC: 3738 AN: 150370 Hom.: 162 Cov.: 32 AF XY: 0.0240 AC XY: 1757 AN XY: 73326

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.00816

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000207

Gnomad4 OTH AF: 0.0159

Alfa AF: 0.00135 Hom.: 1

Bravo AF: 0.0280

Asia WGS AF: 0.00636 AC: 22 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spinocerebellar ataxia type 11 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.28
Dann	Benign	0.47

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: rs78237254; hg19: chr15-43037315;