X-71366346-C-T

Position:

chrX-71366346-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000373790.9(TAF1):c.-29C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,207,491 control chromosomes in the GnomAD database, including 16 homozygotes. There are 412 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 10 hom., 185 hem., cov: 20)

Exomes 𝑓: 0.00076 ( 6 hom. 227 hem. )

Consequence

TAF1
ENST00000373790.9 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.33

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031756163).

BP6

Variant X-71366346-C-T is Benign according to our data. Variant chrX-71366346-C-T is described in ClinVar as [Benign]. Clinvar id is 289208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-71366346-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00691 (758/109723) while in subpopulation AFR AF= 0.0239 (718/29999). AF 95% confidence interval is 0.0225. There are 10 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF1	NM_004606.5 linkuse as main transcript			upstream_gene_variant		ENST00000423759.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF1	ENST00000423759.6 linkuse as main transcript			upstream_gene_variant		5	NM_004606.5	A2

Frequencies

GnomAD3 genomes

AF:

0.00691

AC:

758

AN:

109674

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

185

AN XY:

31888

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00264

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:

0.0000949

Gnomad OTH

AF:

0.00547

GnomAD3 exomes

AF:

0.00202

AC:

371

AN:

183235

Hom.:

AF XY:

0.00125

AC XY:

AN XY:

67821

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000856

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000755

AC:

829

AN:

1097768

Hom.:

Cov.:

AF XY:

0.000625

AC XY:

227

AN XY:

363316

show subpopulations

Gnomad4 AFR exome

AF:

0.0255

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000404

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00691

AC:

758

AN:

109723

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

185

AN XY:

31947

show subpopulations

Gnomad4 AFR

AF:

0.0239

Gnomad4 AMR

AF:

0.00264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000949

Gnomad4 OTH

AF:

0.00540

Alfa

AF:

0.000784

Hom.:

Bravo

AF:

0.00832

ESP6500AA

AF:

0.0256

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00210

AC:

255

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 21, 2016	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

TAF1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.97

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.5

DANN

Benign

0.90

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.44

T;T;T

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.12

N;N;N

REVEL

Benign

0.0030

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.0, 0.0010

.;B;B

Vest4

0.10

MVP

0.082

MPC

0.80

ClinPred

0.00041

GERP RS

-5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.037

gMVP

0.13

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over