X-71516236-CTTTTT-CTTTTTTT

Variant names:

• chrX-71516236-C-CTT
• rs41469947
• ENST00000437147.8:n.1359-12306_1359-12305insTT

Variant summary

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

The ENST00000437147.8(TAF1):​n.1359-12306_1359-12305insTT 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 0.000056 (0 hom., 0 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, 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	NR_104387.2	n.5520-12291_5520-12290dupTT		intron_variant	Intron 38 of 39
TAF1	NR_104388.2	n.5511-12291_5511-12290dupTT		intron_variant	Intron 38 of 39
TAF1	NR_104389.2	n.5418-12291_5418-12290dupTT		intron_variant	Intron 37 of 38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000437147.8	n.1359-12306_1359-12305insTT		intron_variant	Intron 12 of 13	1		ENSP00000406517.4
TAF1	ENST00000462588.5	n.999-12306_999-12305insTT		intron_variant	Intron 9 of 10	1		ENSP00000508350.1
TAF1	ENST00000467309.5	n.*107-12306_*107-12305insTT		intron_variant	Intron 3 of 5	1		ENSP00000507353.1

Frequencies

GnomAD3 genomes AF: 0.0000560 AC: 5 AN: 89352 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000310

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000893

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000560 AC: 5 AN: 89352 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 21702

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24434

American (AMR) AF: 0.00 AC: 0 AN: 7917

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2200

East Asian (EAS) AF: 0.00 AC: 0 AN: 2947

South Asian (SAS) AF: 0.00 AC: 0 AN: 1916

European-Finnish (FIN) AF: 0.000310 AC: 1 AN: 3221

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.0000893 AC: 4 AN: 44811

Other (OTH) AF: 0.00 AC: 0 AN: 1131

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000694), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs41469947; hg19: chrX-70736086;