Genetic Variant TAF1:n.1359-9850_1359-9849insT (chrX-71518692-C-CT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000437147.8(TAF1):n.1359-9850_1359-9849insT 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 0.017 ( 37 hom., 97 hem., cov: 19)

Failed GnomAD Quality Control

Consequence

TAF1
ENST00000437147.8 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

0 publications found

Variant links:

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

TAF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
TAF1	NR_104387.2 link	n.5520-9829dupT	intron_variant	Intron 38 of 39
TAF1	NR_104388.2 link	n.5511-9829dupT	intron_variant	Intron 38 of 39
TAF1	NR_104389.2 link	n.5418-9829dupT	intron_variant	Intron 37 of 38

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
TAF1	ENST00000437147.8 link	n.1359-9850_1359-9849insT	intron_variant	Intron 12 of 13	1	ENSP00000406517.4
TAF1	ENST00000462588.5 link	n.999-9850_999-9849insT	intron_variant	Intron 9 of 10	1	ENSP00000508350.1
TAF1	ENST00000467309.5 link	n.107-9850_107-9849insT	intron_variant	Intron 3 of 5	1	ENSP00000507353.1

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

1346

AN:

79037

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.00758

Gnomad AMR

AF:

0.00593

Gnomad ASJ

AF:

0.00777

Gnomad EAS

AF:

0.0124

Gnomad SAS

AF:

0.00315

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00595

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.0117

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:

0.0170

AC:

1347

AN:

79004

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

AN XY:

18460

show subpopulations

African (AFR)

AF:

0.0387

AC:

814

AN:

21007

American (AMR)

AF:

0.00593

AC:

AN:

7088

Ashkenazi Jewish (ASJ)

AF:

0.00777

AC:

AN:

2058

East Asian (EAS)

AF:

0.0124

AC:

AN:

2414

South Asian (SAS)

AF:

0.00318

AC:

AN:

1570

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

2574

Middle Eastern (MID)

AF:

0.00671

AC:

AN:

149

European-Non Finnish (NFE)

AF:

0.0102

AC:

415

AN:

40584

Other (OTH)

AF:

0.0116

AC:

AN:

1032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00122

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Splicing

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

Publications

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X-71518692-CTTTTTTTTTTT-CTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over