chr20-62006572-CA-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_003185.4(TAF4):c.2160del(p.Val721CysfsTer32) variant causes a frameshift 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 Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TAF4
NM_003185.4 frameshift
NM_003185.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.05
Genes affected
TAF4 (HGNC:11537): (TATA-box binding protein associated factor 4) 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 one of the larger subunits of TFIID that has been shown to potentiate transcriptional activation by retinoic acid, thyroid hormone and vitamin D3 receptors. In addition, this subunit interacts with the transcription factor CREB, which has a glutamine-rich activation domain, and binds to other proteins containing glutamine-rich regions. Aberrant binding to this subunit by proteins with expanded polyglutamine regions has been suggested as one of the pathogenetic mechanisms underlying a group of neurodegenerative disorders referred to as polyglutamine diseases. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAF4 | NM_003185.4 | c.2160del | p.Val721CysfsTer32 | frameshift_variant | 7/15 | ENST00000252996.9 | |
TAF4 | XM_047440429.1 | c.1044del | p.Val349CysfsTer32 | frameshift_variant | 8/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAF4 | ENST00000252996.9 | c.2160del | p.Val721CysfsTer32 | frameshift_variant | 7/15 | 1 | NM_003185.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1440786Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 716388
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
1440786
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30
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0
AN XY:
716388
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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;provider interpretation | Geisinger Autism and Developmental Medicine Institute, Geisinger Health System | Jul 10, 2017 | This 4 year old female was found to carry a de novo variant in the TAF4 gene. This is a gene of uncertain significance; no known human disorders have been clearly associated with this gene. The variant is absent from population databases. This variant causes a frameshift and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. - |
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