X-71452109-AC-A

Position:

• chrX-71452109-AC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004606.5(TAF1):​c.4754-2050del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (346 hom., 1063 hem., cov: 15)
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1	NM_004606.5	c.4754-2050del		intron_variant		ENST00000423759.6	NP_004597.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000423759.6	c.4754-2050del		intron_variant		5	NM_004606.5	ENSP00000406549	A2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 6208 AN: 50333 Hom.: 347 Cov.: 15 AF XY: 0.103 AC XY: 1061 AN XY: 10313

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.0448

Gnomad SAS AF: 0.0382

Gnomad FIN AF: 0.0731

Gnomad MID AF: 0.0941

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 6208 AN: 50324 Hom.: 346 Cov.: 15 AF XY: 0.103 AC XY: 1063 AN XY: 10318

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0807

Gnomad4 EAS AF: 0.0450

Gnomad4 SAS AF: 0.0386

Gnomad4 FIN AF: 0.0731

Gnomad4 NFE AF: 0.0571

Gnomad4 OTH AF: 0.114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs41443746; hg19: chrX-70671959;