X-71445298-CAAAAAAAAAA-CAAAAAAAAA

Variant names:

• chrX-71445298-CA-C
• rs41356545
• NM_004606.5:c.4754-8852delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004606.5(TAF1):​c.4754-8852delA 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 0.15 (146 hom., 265 hem., cov: 18)
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1	NM_004606.5	c.4754-8852delA		intron_variant	Intron 32 of 37	ENST00000423759.6	NP_004597.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000423759.6	c.4754-8871delA		intron_variant	Intron 32 of 37	5	NM_004606.5	ENSP00000406549.2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 5389 AN: 36870 Hom.: 146 Cov.: 18

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00924

Gnomad SAS AF: 0.0779

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.146 AC: 5386 AN: 36878 Hom.: 146 Cov.: 18 AF XY: 0.0495 AC XY: 265 AN XY: 5352

African (AFR) AF: 0.0501 AC: 442 AN: 8817

American (AMR) AF: 0.117 AC: 324 AN: 2768

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 193 AN: 1054

East Asian (EAS) AF: 0.00926 AC: 8 AN: 864

South Asian (SAS) AF: 0.0782 AC: 47 AN: 601

European-Finnish (FIN) AF: 0.177 AC: 161 AN: 912

Middle Eastern (MID) AF: 0.169 AC: 12 AN: 71

European-Non Finnish (NFE) AF: 0.193 AC: 4051 AN: 20997

Other (OTH) AF: 0.165 AC: 82 AN: 497

Alfa AF: 0.0168 Hom.: 49

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.76
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: rs41356545; hg19: chrX-70665148;