X-71518692-CTTTTTTTTTTT-CTTTTTTTTTTTTT

Variant names:

• chrX-71518692-C-CTT
• rs41486346
• ENST00000437147.8:n.1359-9850_1359-9849insTT

Variant summary

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

The ENST00000437147.8(TAF1):​n.1359-9850_1359-9849insTT 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 0.0033 (0 hom., 34 hem., cov: 19)
• Consequence: TAF1 ENST00000437147.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00335 (265/79131) while in subpopulation AFR AF = 0.00989 (208/21041). AF 95% confidence interval is 0.00879. There are 0 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 19. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 34 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1	NR_104387.2		n.5520-9830_5520-9829dupTT		intron	N/A
	TAF1	NR_104388.2		n.5511-9830_5511-9829dupTT		intron	N/A
	TAF1	NR_104389.2		n.5418-9830_5418-9829dupTT		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1	ENST00000437147.8	TSL:1	n.1359-9850_1359-9849insTT		intron	N/A	ENSP00000406517.4
	TAF1	ENST00000462588.5	TSL:1	n.999-9850_999-9849insTT		intron	N/A	ENSP00000508350.1
	TAF1	ENST00000467309.5	TSL:1	n.*107-9850_*107-9849insTT		intron	N/A	ENSP00000507353.1

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 266 AN: 79164 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00994

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000282

Gnomad ASJ AF: 0.000969

Gnomad EAS AF: 0.00165

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.000975

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

GnomAD4 genome AF: 0.00335 AC: 265 AN: 79131 Hom.: 0 Cov.: 19 AF XY: 0.00183 AC XY: 34 AN XY: 18553

African (AFR) AF: 0.00989 AC: 208 AN: 21041

American (AMR) AF: 0.000282 AC: 2 AN: 7089

Ashkenazi Jewish (ASJ) AF: 0.000969 AC: 2 AN: 2065

East Asian (EAS) AF: 0.00165 AC: 4 AN: 2417

South Asian (SAS) AF: 0.000637 AC: 1 AN: 1570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 149

European-Non Finnish (NFE) AF: 0.00113 AC: 46 AN: 40666

Other (OTH) AF: 0.00194 AC: 2 AN: 1032

Alfa AF: 0.00 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs41486346; hg19: chrX-70738542;