X-71504741-C-CAAAAAAAAAAAAAAAAAAAAA

Position:

• chrX-71504741-C-CAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The ENST00000437147.8(TAF1):​c.1361-23789_1361-23769dup variant causes a intron, NMD transcript 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 0.0084 (4 hom., 0 hem., cov: 9)
  • Failed GnomAD Quality Control
• Consequence: TAF1 ENST00000437147.8 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF1	NR_104387.2	n.5520-23789_5520-23769dup		intron_variant, non_coding_transcript_variant
TAF1	NR_104388.2	n.5511-23789_5511-23769dup		intron_variant, non_coding_transcript_variant
TAF1	NR_104389.2	n.5418-23789_5418-23769dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF1	ENST00000437147.8	c.1361-23789_1361-23769dup		intron_variant, NMD_transcript_variant		1
TAF1	ENST00000462588.5	c.1000-23789_1000-23769dup		intron_variant, NMD_transcript_variant		1
TAF1	ENST00000467309.5	c.*106+19760_*106+19780dup		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00839 AC: 48 AN: 5724 Hom.: 4 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 208

Gnomad AFR AF: 0.00372

Gnomad AMI AF: 0.0476

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.00535

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00839 AC: 48 AN: 5724 Hom.: 4 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 208

Gnomad4 AFR AF: 0.00372

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.00535

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0111

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: rs41370846; hg19: chrX-70724591;