X-71504741-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chrX-71504741-C-CAAAAA
• rs41370846
• ENST00000437147.8:n.1359-23801_1359-23800insAAAAA

Variant summary

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

The ENST00000437147.8(TAF1):​n.1359-23801_1359-23800insAAAAA 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 0.045 (3 hom., 0 hem., cov: 9)
• Consequence: TAF1 ENST00000437147.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• 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: G2P, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• X-linked dystonia-parkinsonism

  Inheritance: XL, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 = 0.0528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437147.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1	NR_104387.2		n.5520-23773_5520-23769dupAAAAA		intron	N/A
	TAF1	NR_104388.2		n.5511-23773_5511-23769dupAAAAA		intron	N/A
	TAF1	NR_104389.2		n.5418-23773_5418-23769dupAAAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1	ENST00000437147.8	TSL:1	n.1359-23801_1359-23800insAAAAA		intron	N/A	ENSP00000406517.4	H7C2K9
	TAF1	ENST00000462588.5	TSL:1	n.999-23801_999-23800insAAAAA		intron	N/A	ENSP00000508350.1	A0A804HLH3
	TAF1	ENST00000467309.5	TSL:1	n.*106+19748_*106+19749insAAAAA		intron	N/A	ENSP00000507353.1	A0A804HJ48

Frequencies

GnomAD3 genomes AF: 0.0454 AC: 259 AN: 5709 Hom.: 3 Cov.: 9

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0212

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.0806

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

GnomAD4 genome AF: 0.0454 AC: 259 AN: 5709 Hom.: 3 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 207

African (AFR) AF: 0.0317 AC: 60 AN: 1893

American (AMR) AF: 0.0248 AC: 9 AN: 363

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 4 AN: 189

East Asian (EAS) AF: 0.0245 AC: 5 AN: 204

South Asian (SAS) AF: 0.0465 AC: 2 AN: 43

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 64

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.0601 AC: 172 AN: 2862

Other (OTH) AF: 0.0781 AC: 5 AN: 64

Alfa AF: 0.0139 Hom.: 37

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41370846; hg19: chrX-70724591;