chrX-71366421-TTTC-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_004606.5(TAF1):c.50_52del(p.Ser17del) variant causes a inframe deletion change. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 20)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control
Consequence
TAF1
NM_004606.5 inframe_deletion
NM_004606.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.35
Genes affected
TAF1 (HGNC:11535): (TATA-box binding protein associated factor 1) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is the basal transcription factor 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 the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent protein kinase domains at the N- and C-terminals, but also possesses acetyltransferase activity and can act as a ubiquitin-activating/conjugating enzyme. Mutations in this gene result in Dystonia 3, torsion, X-linked, a dystonia-parkinsonism disorder. Alternative splicing of this gene results in multiple transcript variants. This gene is part of a complex transcription unit (TAF1/DYT3), wherein some transcript variants share exons with TAF1 as well as additional downstream DYT3 exons. [provided by RefSeq, Oct 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_004606.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAF1 | NM_004606.5 | c.50_52del | p.Ser17del | inframe_deletion | 1/38 | ENST00000423759.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAF1 | ENST00000423759.6 | c.50_52del | p.Ser17del | inframe_deletion | 1/38 | 5 | NM_004606.5 | A2 |
Frequencies
GnomAD3 genomes Cov.: 20
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183155Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67715
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000182 AC: 2AN: 1097977Hom.: 0 AF XY: 0.00000275 AC XY: 1AN XY: 363371
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome Cov.: 20
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with TAF1-related conditions. This variant is present in population databases (rs757925911, gnomAD no frequency). This variant, c.110_112del, results in the deletion of 1 amino acid(s) of the TAF1 protein (p.Ser37del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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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