rs55736770
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_003194.5(TBP):āc.216A>Gā(p.Gln72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. QQ72Q?) has been classified as Benign.
Frequency
Genomes: š 0.43 ( 396 hom., cov: 0)
Exomes š: 0.22 ( 2037 hom. )
Failed GnomAD Quality Control
Consequence
TBP
NM_003194.5 synonymous
NM_003194.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0240
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 6-170561952-A-G is Benign according to our data. Variant chr6-170561952-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 130558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-170561952-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.024 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBP | NM_003194.5 | c.216A>G | p.Gln72= | synonymous_variant | 3/8 | ENST00000392092.7 | |
TBP | NM_001172085.2 | c.156A>G | p.Gln52= | synonymous_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBP | ENST00000392092.7 | c.216A>G | p.Gln72= | synonymous_variant | 3/8 | 1 | NM_003194.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 9072AN: 21320Hom.: 397 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.0256 AC: 3139AN: 122506Hom.: 14 AF XY: 0.0246 AC XY: 1610AN XY: 65532
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.221 AC: 40358AN: 182754Hom.: 2037 Cov.: 0 AF XY: 0.227 AC XY: 20689AN XY: 91106
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GnomAD4 genome ? Data not reliable, filtered out with message: InbreedingCoeff AF: 0.426 AC: 9067AN: 21308Hom.: 396 Cov.: 0 AF XY: 0.421 AC XY: 4229AN XY: 10042
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spinocerebellar ataxia type 17 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 10, 2014 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 27, 2014 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | - - |
Computational scores
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Name
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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