chrX-71366346-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000373790.9(TAF1):c.-29C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,207,491 control chromosomes in the GnomAD database, including 16 homozygotes. There are 412 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0069 ( 10 hom., 185 hem., cov: 20)
Exomes 𝑓: 0.00076 ( 6 hom. 227 hem. )
Consequence
TAF1
ENST00000373790.9 5_prime_UTR
ENST00000373790.9 5_prime_UTR
Scores
1
14
Clinical Significance
Conservation
PhyloP100: -1.33
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0031756163).
BP6
Variant X-71366346-C-T is Benign according to our data. Variant chrX-71366346-C-T is described in ClinVar as [Benign]. Clinvar id is 289208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-71366346-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00691 (758/109723) while in subpopulation AFR AF= 0.0239 (718/29999). AF 95% confidence interval is 0.0225. There are 10 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAF1 | NM_004606.5 | upstream_gene_variant | ENST00000423759.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAF1 | ENST00000423759.6 | upstream_gene_variant | 5 | NM_004606.5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00691 AC: 758AN: 109674Hom.: 10 Cov.: 20 AF XY: 0.00580 AC XY: 185AN XY: 31888
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GnomAD3 exomes AF: 0.00202 AC: 371AN: 183235Hom.: 4 AF XY: 0.00125 AC XY: 85AN XY: 67821
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GnomAD4 exome AF: 0.000755 AC: 829AN: 1097768Hom.: 6 Cov.: 33 AF XY: 0.000625 AC XY: 227AN XY: 363316
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GnomAD4 genome AF: 0.00691 AC: 758AN: 109723Hom.: 10 Cov.: 20 AF XY: 0.00579 AC XY: 185AN XY: 31947
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 21, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
TAF1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 19, 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.0, 0.0010
.;B;B
Vest4
MVP
MPC
0.80
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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