GeneBe

ENST00000437147.8:n.*247C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000437147.8(TAF1):​n.*247C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 112,177 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Consequence

TAF1
ENST00000437147.8 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.11

Publications

3 publications found
Variant links:
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]
SOCS6P1 (HGNC:54990): (SOCS6 pseudogene 1)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAF1NR_104387.2 linkn.5776C>A non_coding_transcript_exon_variant Exon 40 of 40
TAF1NR_104388.2 linkn.5767C>A non_coding_transcript_exon_variant Exon 40 of 40
TAF1NR_104389.2 linkn.5674C>A non_coding_transcript_exon_variant Exon 39 of 39

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAF1ENST00000437147.8 linkn.*247C>A non_coding_transcript_exon_variant Exon 14 of 14 1 ENSP00000406517.4 H7C2K9
TAF1ENST00000462588.5 linkn.*247C>A non_coding_transcript_exon_variant Exon 11 of 11 1 ENSP00000508350.1 A0A804HLH3
TAF1ENST00000467309.5 linkn.*363C>A non_coding_transcript_exon_variant Exon 5 of 6 1 ENSP00000507353.1 A0A804HJ48

Frequencies

GnomAD3 genomes
AF:
0.00000891
AC:
1
AN:
112177
Hom.:
0
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
0
GnomAD4 genome
AF:
0.00000891
AC:
1
AN:
112177
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34325
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
30864
American (AMR)
AF:
0.00
AC:
0
AN:
10600
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2654
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3582
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2701
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6073
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
240
European-Non Finnish (NFE)
AF:
0.0000188
AC:
1
AN:
53260
Other (OTH)
AF:
0.00
AC:
0
AN:
1513
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.43
DANN
Benign
0.53
PhyloP100
-4.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs397509359; hg19: chrX-70749635; API