rs796868804
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_003194.5(TBP):c.233_234insACAGCA(p.Gln77_Gln78dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00000226 in 883,536 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000079 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000013 ( 0 hom. )
Consequence
TBP
NM_003194.5 disruptive_inframe_insertion
NM_003194.5 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.78
Publications
2 publications found
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]
TBP Gene-Disease associations (from GenCC):
- spinocerebellar ataxia type 17Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
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.233_234insACAGCA | p.Gln77_Gln78dup | disruptive_inframe_insertion | Exon 3 of 8 | ENST00000392092.7 | NP_003185.1 | |
| TBP | NM_001172085.2 | c.173_174insACAGCA | p.Gln57_Gln58dup | disruptive_inframe_insertion | Exon 2 of 7 | NP_001165556.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000787 AC: 1AN: 127018Hom.: 0 Cov.: 28 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
127018
Hom.:
Cov.:
28
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000132 AC: 1AN: 756450Hom.: 0 Cov.: 0 AF XY: 0.00000267 AC XY: 1AN XY: 374038 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
756450
Hom.:
Cov.:
0
AF XY:
AC XY:
1
AN XY:
374038
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
8368
American (AMR)
AF:
AC:
0
AN:
16484
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
10240
East Asian (EAS)
AF:
AC:
1
AN:
15136
South Asian (SAS)
AF:
AC:
0
AN:
41590
European-Finnish (FIN)
AF:
AC:
0
AN:
27178
Middle Eastern (MID)
AF:
AC:
0
AN:
2612
European-Non Finnish (NFE)
AF:
AC:
0
AN:
603832
Other (OTH)
AF:
AC:
0
AN:
31010
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000787 AC: 1AN: 127086Hom.: 0 Cov.: 28 AF XY: 0.0000163 AC XY: 1AN XY: 61534 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
127086
Hom.:
Cov.:
28
AF XY:
AC XY:
1
AN XY:
61534
show subpopulations
African (AFR)
AF:
AC:
0
AN:
35314
American (AMR)
AF:
AC:
0
AN:
12548
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2850
East Asian (EAS)
AF:
AC:
1
AN:
4486
South Asian (SAS)
AF:
AC:
0
AN:
3764
European-Finnish (FIN)
AF:
AC:
0
AN:
8802
Middle Eastern (MID)
AF:
AC:
0
AN:
248
European-Non Finnish (NFE)
AF:
AC:
0
AN:
56592
Other (OTH)
AF:
AC:
0
AN:
1684
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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