rs41384445

chrX-71372432-CAAAAAAAAAAAAAA-CchrX-71372432-CAAAAAAAAAAAAAA-CAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAchrX-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004606.5(TAF1):c.353-2722_353-2709del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 28,537 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00014 (0 hom., 2 hem., cov: 0)
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF1	NM_004606.5	c.353-2722_353-2709del		intron_variant		ENST00000423759.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF1	ENST00000423759.6	c.353-2722_353-2709del		intron_variant		5	NM_004606.5	A2

Frequencies

GnomAD3 genomes AF: 0.000140 AC: 4 AN: 28537 Hom.: 0 Cov.: 0 AF XY: 0.00185 AC XY: 2 AN XY: 1081

Gnomad AFR AF: 0.000613

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: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000140 AC: 4 AN: 28537 Hom.: 0 Cov.: 0 AF XY: 0.00185 AC XY: 2 AN XY: 1081

Gnomad4 AFR AF: 0.000613

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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: rs41384445; hg19: chrX-70592282;