chrX-71366461-C-G
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_004606.5(TAF1):c.87C>G(p.Ala29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 941,126 control chromosomes in the GnomAD database, including 17 homozygotes. There are 1,841 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0065 ( 3 hom., 100 hem., cov: 15)
Exomes 𝑓: 0.0062 ( 14 hom. 1741 hem. )
Consequence
TAF1
NM_004606.5 synonymous
NM_004606.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.713
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 Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant X-71366461-C-G is Benign according to our data. Variant chrX-71366461-C-G is described in ClinVar as [Benign]. Clinvar id is 695433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-71366461-C-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.713 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00654 (451/68985) while in subpopulation NFE AF= 0.00736 (282/38323). AF 95% confidence interval is 0.00665. There are 3 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 15. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAF1 | NM_004606.5 | c.87C>G | p.Ala29= | synonymous_variant | 1/38 | ENST00000423759.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAF1 | ENST00000423759.6 | c.87C>G | p.Ala29= | synonymous_variant | 1/38 | 5 | NM_004606.5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00655 AC: 452AN: 68956Hom.: 3 Cov.: 15 AF XY: 0.00683 AC XY: 100AN XY: 14646
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GnomAD3 exomes AF: 0.00443 AC: 709AN: 160005Hom.: 2 AF XY: 0.00462 AC XY: 261AN XY: 56499
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GnomAD4 exome AF: 0.00625 AC: 5448AN: 872141Hom.: 14 Cov.: 33 AF XY: 0.00623 AC XY: 1741AN XY: 279345
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
TAF1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 08, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at