Genetic Variant TAF1:c.-165A>C (chrX-71366210-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004606.5(TAF1):c.-165A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 656 hom., 1239 hem., cov: 0)

Exomes 𝑓: 0.072 ( 233 hom. 861 hem. )

Consequence

TAF1
NM_004606.5 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -7.38

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant X-71366210-A-C is Benign according to our data. Variant chrX-71366210-A-C is described in ClinVar as [Benign]. Clinvar id is 1227807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1	NM_004606.5 link	c.-165A>C		upstream_gene_variant		ENST00000423759.6	NP_004597.3	P21675

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1	ENST00000423759.6 link	c.-165A>C		upstream_gene_variant		5	NM_004606.5	ENSP00000406549.2		P21675

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

7377

AN:

26062

Hom.:

656

Cov.:

AF XY:

0.223

AC XY:

1223

AN XY:

5476

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.0204

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.0313

Gnomad EAS

AF:

0.00778

Gnomad SAS

AF:

0.0639

Gnomad FIN

AF:

0.0316

Gnomad MID

AF:

0.0467

Gnomad NFE

AF:

0.0535

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.0719

AC:

8309

AN:

115583

Hom.:

233

Cov.:

AF XY:

0.0360

AC XY:

861

AN XY:

23909

show subpopulations

Gnomad4 AFR exome

AF:

0.367

Gnomad4 AMR exome

AF:

0.0791

Gnomad4 ASJ exome

AF:

0.0331

Gnomad4 EAS exome

AF:

0.00805

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.0556

Gnomad4 NFE exome

AF:

0.0525

Gnomad4 OTH exome

AF:

0.0880

GnomAD4 genome

AF:

0.283

AC:

7397

AN:

26097

Hom.:

656

Cov.:

AF XY:

0.225

AC XY:

1239

AN XY:

5497

show subpopulations

Gnomad4 AFR

AF:

0.499

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.0313

Gnomad4 EAS

AF:

0.00778

Gnomad4 SAS

AF:

0.0615

Gnomad4 FIN

AF:

0.0316

Gnomad4 NFE

AF:

0.0535

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.0703

Hom.:

267

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 22, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.67

DANN

Benign

0.19

Splicing

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