chr15-42745610-T-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_173500.4(TTBK2):c.*185A>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 0.000238 in 726,474 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )
Consequence
TTBK2
NM_173500.4 3_prime_UTR
NM_173500.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.26
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 15-42745610-T-C is Benign according to our data. Variant chr15-42745610-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 884242.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000348 (53/152376) while in subpopulation EAS AF= 0.00404 (21/5192). AF 95% confidence interval is 0.00271. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 53 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTBK2 | NM_173500.4 | c.*185A>G | 3_prime_UTR_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.*185A>G | 3_prime_UTR_variant | 15/15 | 5 | NM_173500.4 | ENSP00000267890 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000348 AC: 53AN: 152258Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000209 AC: 120AN: 574098Hom.: 1 Cov.: 8 AF XY: 0.000197 AC XY: 59AN XY: 299068
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GnomAD4 genome AF: 0.000348 AC: 53AN: 152376Hom.: 0 Cov.: 32 AF XY: 0.000335 AC XY: 25AN XY: 74518
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spinocerebellar ataxia type 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at