X-71431003-ATTTTTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTT

Position:

• chrX-71431003-ATTTTTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004606.5(TAF1):​c.4753+6793_4753+6794dup 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 0.0066 (29 hom., 66 hem., cov: 15)
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00665 (456/68584) while in subpopulation NFE AF= 0.00901 (345/38280). AF 95% confidence interval is 0.00823. There are 29 homozygotes in gnomad4. There are 66 alleles in male gnomad4 subpopulation. Median coverage is 15. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1	NM_004606.5	c.4753+6793_4753+6794dup		intron_variant		ENST00000423759.6	NP_004597.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000423759.6	c.4753+6793_4753+6794dup		intron_variant		5	NM_004606.5	ENSP00000406549	A2

Frequencies

GnomAD3 genomes AF: 0.00665 AC: 456 AN: 68590 Hom.: 29 Cov.: 15 AF XY: 0.00412 AC XY: 66 AN XY: 16034

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.0566

Gnomad AMR AF: 0.00619

Gnomad ASJ AF: 0.00372

Gnomad EAS AF: 0.00227

Gnomad SAS AF: 0.00321

Gnomad FIN AF: 0.000797

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00901

Gnomad OTH AF: 0.00494

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

GnomAD4 genome AF: 0.00665 AC: 456 AN: 68584 Hom.: 29 Cov.: 15 AF XY: 0.00412 AC XY: 66 AN XY: 16032

Gnomad4 AFR AF: 0.00193

Gnomad4 AMR AF: 0.00618

Gnomad4 ASJ AF: 0.00372

Gnomad4 EAS AF: 0.00228

Gnomad4 SAS AF: 0.00324

Gnomad4 FIN AF: 0.000797

Gnomad4 NFE AF: 0.00901

Gnomad4 OTH AF: 0.00491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41481947; hg19: chrX-70650853;