X-71516236-CTTTTT-CTTTTTT

Variant names:

• chrX-71516236-C-CT
• rs41469947
• ENST00000437147.8:n.1359-12306_1359-12305insT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000437147.8(TAF1):​n.1359-12306_1359-12305insT 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 0.0082 (12 hom., 95 hem., cov: 19)
• Consequence: TAF1 ENST00000437147.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• 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, G2P, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• X-linked dystonia-parkinsonism

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

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00824 (736/89315) while in subpopulation AFR AF = 0.0254 (622/24450). AF 95% confidence interval is 0.0238. There are 12 homozygotes in GnomAd4. There are 95 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 XL,Unknown gene

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.5520-12290dupT		intron	N/A
	TAF1	NR_104388.2		n.5511-12290dupT		intron	N/A
	TAF1	NR_104389.2		n.5418-12290dupT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1	ENST00000437147.8	TSL:1	n.1359-12306_1359-12305insT		intron	N/A	ENSP00000406517.4	H7C2K9
	TAF1	ENST00000462588.5	TSL:1	n.999-12306_999-12305insT		intron	N/A	ENSP00000508350.1	A0A804HLH3
	TAF1	ENST00000467309.5	TSL:1	n.*107-12306_*107-12305insT		intron	N/A	ENSP00000507353.1	A0A804HJ48

Frequencies

GnomAD3 genomes AF: 0.00824 AC: 736 AN: 89324 Hom.: 12 Cov.: 19

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.00174

Gnomad AMR AF: 0.00303

Gnomad ASJ AF: 0.000455

Gnomad EAS AF: 0.000679

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00500

Gnomad NFE AF: 0.00158

Gnomad OTH AF: 0.00619

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

GnomAD4 genome AF: 0.00824 AC: 736 AN: 89315 Hom.: 12 Cov.: 19 AF XY: 0.00438 AC XY: 95 AN XY: 21701

African (AFR) AF: 0.0254 AC: 622 AN: 24450

American (AMR) AF: 0.00303 AC: 24 AN: 7922

Ashkenazi Jewish (ASJ) AF: 0.000455 AC: 1 AN: 2200

East Asian (EAS) AF: 0.000682 AC: 2 AN: 2933

South Asian (SAS) AF: 0.00 AC: 0 AN: 1900

European-Finnish (FIN) AF: 0.00217 AC: 7 AN: 3221

Middle Eastern (MID) AF: 0.00556 AC: 1 AN: 180

European-Non Finnish (NFE) AF: 0.00159 AC: 71 AN: 44793

Other (OTH) AF: 0.00613 AC: 7 AN: 1141

Alfa AF: 0.000870 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41469947;

hg19: chrX-70736086;