X-71397593-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004606.5(TAF1):c.3620+127A>G variant causes a intron 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 0.98 (37078 hom., 31281 hem., cov: 22)
  • Exomes 𝑓: 0.97 (240259 hom. 190481 hem.)
  • Failed GnomAD Quality Control
• Consequence: TAF1 NM_004606.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant X-71397593-A-G is Benign according to our data. Variant chrX-71397593-A-G is described in ClinVar as [Benign]. Clinvar id is 1278289.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71397593-A-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF1	NM_004606.5	c.3620+127A>G		intron_variant		ENST00000423759.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF1	ENST00000423759.6	c.3620+127A>G		intron_variant		5	NM_004606.5	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 107172 AN: 109690 Hom.: 37081 Cov.: 22 AF XY: 0.979 AC XY: 31218 AN XY: 31894 FAILED QC

Gnomad AFR AF: 0.995

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.970

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.973 AC: 685508 AN: 704853 Hom.: 240259 AF XY: 0.978 AC XY: 190481 AN XY: 194821

Gnomad4 AFR exome AF: 0.995

Gnomad4 AMR exome AF: 0.986

Gnomad4 ASJ exome AF: 0.975

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.989

Gnomad4 FIN exome AF: 0.979

Gnomad4 NFE exome AF: 0.968

Gnomad4 OTH exome AF: 0.972

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.977 AC: 107227 AN: 109743 Hom.: 37078 Cov.: 22 AF XY: 0.979 AC XY: 31281 AN XY: 31957

Gnomad4 AFR AF: 0.995

Gnomad4 AMR AF: 0.969

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.970

Alfa AF: 0.951 Hom.: 3209

Bravo AF: 0.978

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.92
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs5980760; hg19: chrX-70617443;