rs1023021

Positions:

• chrX-71508088-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NR_104387.2(TAF1):​n.5520-20454A>C variant causes a intron, non coding transcript 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 NR_104387.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.07

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1	NR_104387.2	n.5520-20454A>C		intron_variant, non_coding_transcript_variant
TAF1	NR_104388.2	n.5511-20454A>C		intron_variant, non_coding_transcript_variant
TAF1	NR_104389.2	n.5418-20454A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000437147.8	c.1361-20454A>C		intron_variant, NMD_transcript_variant		1		ENSP00000406517
TAF1	ENST00000462588.5	c.1000-20454A>C		intron_variant, NMD_transcript_variant		1		ENSP00000508350
TAF1	ENST00000467309.5	c.*107-20454A>C		intron_variant, NMD_transcript_variant		1		ENSP00000507353

Frequencies

GnomAD3 genomes AF: 0.687 AC: 48867 AN: 71145 Hom.: 13887 Cov.: 11 AF XY: 0.616 AC XY: 6297 AN XY: 10229

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

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.701

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1023021; hg19: chrX-70727938;