X-71445298-CAAAAAAAAAA-CAAAAAAAAAAA

Position:

• chrX-71445298-CAAAAAAAAAA-CAAAAAAAAAAA

Variant summary

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

The NM_004606.5(TAF1):​c.4754-8852dupA 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 0.024 (17 hom., 62 hem., cov: 18)
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

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]

TAF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0241 (881/36487) while in subpopulation NFE AF= 0.0303 (629/20776). AF 95% confidence interval is 0.0283. There are 17 homozygotes in gnomad4. There are 62 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1	NM_004606.5	c.4754-8852dupA		intron_variant		ENST00000423759.6	NP_004597.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000423759.6	c.4754-8852dupA		intron_variant		5	NM_004606.5	ENSP00000406549.2

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 881 AN: 36479 Hom.: 17 Cov.: 18 AF XY: 0.0114 AC XY: 62 AN XY: 5425

Gnomad AFR AF: 0.00829

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00192

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0951

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.00616

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

GnomAD4 genome AF: 0.0241 AC: 881 AN: 36487 Hom.: 17 Cov.: 18 AF XY: 0.0114 AC XY: 62 AN XY: 5429

Gnomad4 AFR AF: 0.00828

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.00192

Gnomad4 EAS AF: 0.0117

Gnomad4 SAS AF: 0.00167

Gnomad4 FIN AF: 0.0951

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.00609

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: rs41356545; hg19: chrX-70665148;