rs1023021

Variant names:

• chrX-71508088-A-C
• rs1023021
• ENST00000437147.8:n.1359-20454A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000437147.8(TAF1):​n.1359-20454A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (13885 hom., 6293 hem., cov: 11)
  • Failed GnomAD Quality Control
• Consequence: TAF1 ENST00000437147.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.07
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1	NR_104387.2	n.5520-20454A>C		intron_variant	Intron 38 of 39
TAF1	NR_104388.2	n.5511-20454A>C		intron_variant	Intron 38 of 39
TAF1	NR_104389.2	n.5418-20454A>C		intron_variant	Intron 37 of 38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000437147.8	n.1359-20454A>C		intron_variant	Intron 12 of 13	1		ENSP00000406517.4
TAF1	ENST00000462588.5	n.999-20454A>C		intron_variant	Intron 9 of 10	1		ENSP00000508350.1
TAF1	ENST00000467309.5	n.*107-20454A>C		intron_variant	Intron 3 of 5	1		ENSP00000507353.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 48867 AN: 71145 Hom.: 13887 Cov.: 11

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.699

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: InbreedingCoeff AF: 0.687 AC: 48848 AN: 71117 Hom.: 13885 Cov.: 11 AF XY: 0.615 AC XY: 6293 AN XY: 10229

African (AFR) AF: 0.643 AC: 11568 AN: 17987

American (AMR) AF: 0.773 AC: 4839 AN: 6262

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 1389 AN: 1960

East Asian (EAS) AF: 0.740 AC: 1674 AN: 2263

South Asian (SAS) AF: 0.706 AC: 915 AN: 1296

European-Finnish (FIN) AF: 0.647 AC: 1126 AN: 1740

Middle Eastern (MID) AF: 0.747 AC: 109 AN: 146

European-Non Finnish (NFE) AF: 0.689 AC: 26203 AN: 38046

Other (OTH) AF: 0.701 AC: 662 AN: 944

Alfa AF: 0.667 Hom.: 3236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.035
DANN	Benign	0.32
PhyloP100		-4.1

Splicing

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

Other links and lift over

dbSNP: rs1023021; hg19: chrX-70727938;