chr20-62006648-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_003185.4(TAF4):c.2085C>T(p.Ala695=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,599,954 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
TAF4
NM_003185.4 synonymous
NM_003185.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.45
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 Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 20-62006648-G-A is Benign according to our data. Variant chr20-62006648-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652463.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.45 with no splicing effect.
BS2
?
High AC in GnomAd at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAF4 | NM_003185.4 | c.2085C>T | p.Ala695= | synonymous_variant | 7/15 | ENST00000252996.9 | |
TAF4 | XM_047440429.1 | c.969C>T | p.Ala323= | synonymous_variant | 8/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAF4 | ENST00000252996.9 | c.2085C>T | p.Ala695= | synonymous_variant | 7/15 | 1 | NM_003185.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152132Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000130 AC: 31AN: 237850Hom.: 0 AF XY: 0.000146 AC XY: 19AN XY: 129836
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GnomAD4 exome AF: 0.000164 AC: 238AN: 1447704Hom.: 1 Cov.: 30 AF XY: 0.000174 AC XY: 125AN XY: 718864
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | TAF4: BP4, BP7 - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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