rs376543555
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_173500.4(TTBK2):āc.1929T>Cā(p.Ala643=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,614,212 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.00060 ( 0 hom., cov: 32)
Exomes š: 0.000065 ( 0 hom. )
Consequence
TTBK2
NM_173500.4 synonymous
NM_173500.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.51
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 15-42775204-A-G is Benign according to our data. Variant chr15-42775204-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 448752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.51 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000604 (92/152342) while in subpopulation AFR AF= 0.00214 (89/41586). AF 95% confidence interval is 0.00178. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 92 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTBK2 | NM_173500.4 | c.1929T>C | p.Ala643= | synonymous_variant | 13/15 | ENST00000267890.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTBK2 | ENST00000267890.11 | c.1929T>C | p.Ala643= | synonymous_variant | 13/15 | 5 | NM_173500.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000611 AC: 93AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000116 AC: 29AN: 249436Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135344
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GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 727244
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GnomAD4 genome ? AF: 0.000604 AC: 92AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | TTBK2: BP4 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at