NM_004606.5:c.4754-2050dupC

Variant names:

• chrX-71452109-A-AC
• rs41443746
• NM_004606.5:c.4754-2050dupC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004606.5(TAF1):​c.4754-2050dupC 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 0.070 (109 hom., 487 hem., cov: 15)
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• 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: G2P, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• X-linked dystonia-parkinsonism

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

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004606.5. 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	NM_004606.5	MANE Select	c.4754-2050dupC		intron	N/A	NP_004597.3
	TAF1	NM_001286074.2		c.4754-2050dupC		intron	N/A	NP_001273003.2
	TAF1	NM_001440852.1		c.4754-2050dupC		intron	N/A	NP_001427781.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1	ENST00000423759.6	TSL:5 MANE Select	c.4754-2061_4754-2060insC		intron	N/A	ENSP00000406549.2	P21675-14
	TAF1	ENST00000373790.9	TSL:1	c.4691-2061_4691-2060insC		intron	N/A	ENSP00000362895.5	P21675-13
	TAF1	ENST00000437147.8	TSL:1	n.713-2061_713-2060insC		intron	N/A	ENSP00000406517.4	H7C2K9

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 3537 AN: 50533 Hom.: 109 Cov.: 15

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.0853

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

GnomAD4 genome AF: 0.0700 AC: 3538 AN: 50525 Hom.: 109 Cov.: 15 AF XY: 0.0468 AC XY: 487 AN XY: 10415

African (AFR) AF: 0.0429 AC: 634 AN: 14793

American (AMR) AF: 0.0906 AC: 396 AN: 4373

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 120 AN: 1291

East Asian (EAS) AF: 0.0103 AC: 16 AN: 1556

South Asian (SAS) AF: 0.0254 AC: 25 AN: 986

European-Finnish (FIN) AF: 0.0511 AC: 104 AN: 2037

Middle Eastern (MID) AF: 0.125 AC: 9 AN: 72

European-Non Finnish (NFE) AF: 0.0888 AC: 2172 AN: 24446

Other (OTH) AF: 0.0860 AC: 56 AN: 651

Alfa AF: 0.00297 Hom.: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs41443746; hg19: chrX-70671959;