X-71372432-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chrX-71372432-CA-C
• rs41384445
• NM_004606.5:c.353-2709delA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004606.5(TAF1):​c.353-2709delA 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 0.49 (995 hom., 57 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked, syndromic 33

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Illumina
• X-linked dystonia-parkinsonism

  Inheritance: XL, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• X-linked intellectual disability-global development delay-facial dysmorphism-sacral caudal remnant syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1	NM_004606.5	c.353-2709delA		intron_variant	Intron 3 of 37	ENST00000423759.6	NP_004597.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000423759.6	c.353-2734delA		intron_variant	Intron 3 of 37	5	NM_004606.5	ENSP00000406549.2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 13715 AN: 27816 Hom.: 998 Cov.: 0

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.529

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;InbreedingCoeff AF: 0.493 AC: 13709 AN: 27826 Hom.: 995 Cov.: 0 AF XY: 0.167 AC XY: 57 AN XY: 342

African (AFR) AF: 0.453 AC: 2902 AN: 6413

American (AMR) AF: 0.575 AC: 901 AN: 1566

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 428 AN: 880

East Asian (EAS) AF: 0.566 AC: 373 AN: 659

South Asian (SAS) AF: 0.589 AC: 116 AN: 197

European-Finnish (FIN) AF: 0.649 AC: 96 AN: 148

Middle Eastern (MID) AF: 0.676 AC: 23 AN: 34

European-Non Finnish (NFE) AF: 0.494 AC: 8592 AN: 17403

Other (OTH) AF: 0.528 AC: 161 AN: 305

Alfa AF: 0.160 Hom.: 186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41384445; hg19: chrX-70592282;