chr6-170561925-A-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAACAACAACAG
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP3
The NM_003194.5(TBP):c.215_216insGCAACAACAACAGCAGCAGCAGCAGCAGCAGCAGCAGCA(p.Gln60_Gln72dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q72Q) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 0)
Consequence
TBP
NM_003194.5 disruptive_inframe_insertion
NM_003194.5 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.40
Genes affected
TBP (HGNC:11588): (TATA-box binding protein) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes TBP, the TATA-binding protein. A distinctive feature of TBP is a long string of glutamines in the N-terminus. This region of the protein modulates the DNA binding activity of the C terminus, and modulation of DNA binding affects the rate of transcription complex formation and initiation of transcription. The number of CAG repeats encoding the polyglutamine tract is usually 25-42, and expansion of the number of repeats to 45-66 increases the length of the polyglutamine string and is associated with spinocerebellar ataxia 17, a neurodegenerative disorder classified as a polyglutamine disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-170561925-A-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAACAACAACAG is Pathogenic according to our data. Variant chr6-170561925-A-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAACAACAACAG is described in ClinVar as [Pathogenic]. Clinvar id is 3572894.Status of the report is criteria_provided_single_submitter, 1 stars.
BP3
Nonframeshift variant in repetitive region in NM_003194.5
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TBP | NM_003194.5 | c.215_216insGCAACAACAACAGCAGCAGCAGCAGCAGCAGCAGCAGCA | p.Gln60_Gln72dup | disruptive_inframe_insertion | Exon 3 of 8 | ENST00000392092.7 | NP_003185.1 | |
| TBP | NM_001172085.2 | c.155_156insGCAACAACAACAGCAGCAGCAGCAGCAGCAGCAGCAGCA | p.Gln40_Gln52dup | disruptive_inframe_insertion | Exon 2 of 7 | NP_001165556.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
0
GnomAD4 exome Cov.: 79
GnomAD4 exome
Cov.:
79
GnomAD4 genome
GnomAD4 genome
Cov.:
0
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spinocerebellar ataxia type 17 Pathogenic:1
Dec 18, 2024
Institute of Human Genetics, University of Leipzig Medical Center
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.