X-71372432-C-CAAA

Variant names:

• chrX-71372432-C-CAAA
• rs41384445
• NM_004606.5:c.353-2711_353-2709dupAAA

Variant summary

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

The NM_004606.5(TAF1):​c.353-2711_353-2709dupAAA 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 0.000035 (0 hom., 0 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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: 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: Uncertain_significance. The variant received 0 ACMG points.

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.353-2711_353-2709dupAAA		intron	N/A	NP_004597.3
	TAF1	NM_001286074.2		c.353-2711_353-2709dupAAA		intron	N/A	NP_001273003.2
	TAF1	NM_001440852.1		c.353-2711_353-2709dupAAA		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.353-2735_353-2734insAAA		intron	N/A	ENSP00000406549.2	P21675-14
	TAF1	ENST00000373790.9	TSL:1	c.353-2735_353-2734insAAA		intron	N/A	ENSP00000362895.5	P21675-13
	TAF1	ENST00000683782.1		c.353-2735_353-2734insAAA		intron	N/A	ENSP00000506996.1	A0A804HIC2

Frequencies

GnomAD3 genomes AF: 0.0000350 AC: 1 AN: 28534 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000153

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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: AS_VQSR AF: 0.0000350 AC: 1 AN: 28534 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1080

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

African (AFR) AF: 0.000153 AC: 1 AN: 6530

American (AMR) AF: 0.00 AC: 0 AN: 1595

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 921

East Asian (EAS) AF: 0.00 AC: 0 AN: 692

South Asian (SAS) AF: 0.00 AC: 0 AN: 203

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 39

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 17859

Other (OTH) AF: 0.00 AC: 0 AN: 303

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41384445; hg19: chrX-70592282;