chrX-71397593-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.410

Publications

1 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: Benign. The variant received -12 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 VariationId is 1278289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TAF1	NM_004606.5	MANE Select	c.3620+127A>G	intron	N/A	NP_004597.3
TAF1	NM_001286074.2		c.3620+127A>G	intron	N/A	NP_001273003.2
TAF1	NM_001440852.1		c.3620+127A>G	intron	N/A	NP_001427781.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TAF1	ENST00000423759.6	TSL:5 MANE Select	c.3620+127A>G	intron	N/A	ENSP00000406549.2
TAF1	ENST00000373790.9	TSL:1	c.3557+127A>G	intron	N/A	ENSP00000362895.5
TAF1	ENST00000683782.1		c.3620+127A>G	intron	N/A	ENSP00000506996.1

Frequencies

GnomAD3 genomes

AF:

0.977

AC:

107172

AN:

109690

Hom.:

37081

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.995

AC:

17695

AN:

17781

American (AMR)

AF:

0.986

AC:

23001

AN:

23339

Ashkenazi Jewish (ASJ)

AF:

0.975

AC:

13427

AN:

13771

East Asian (EAS)

AF:

1.00

AC:

26250

AN:

26250

South Asian (SAS)

AF:

0.989

AC:

37225

AN:

37650

European-Finnish (FIN)

AF:

0.979

AC:

35705

AN:

36456

Middle Eastern (MID)

AF:

0.968

AC:

3047

AN:

3148

European-Non Finnish (NFE)

AF:

0.968

AC:

497657

AN:

514063

Other (OTH)

AF:

0.972

AC:

31501

AN:

32395

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

735

1470

2206

2941

3676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10352

20704

31056

41408

51760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.977

AC:

107227

AN:

109743

Hom.:

37078

Cov.:

AF XY:

0.979

AC XY:

31281

AN XY:

31957

show subpopulations

African (AFR)

AF:

0.995

AC:

29966

AN:

30110

American (AMR)

AF:

0.969

AC:

9857

AN:

10171

Ashkenazi Jewish (ASJ)

AF:

0.977

AC:

2573

AN:

2634

East Asian (EAS)

AF:

0.999

AC:

3501

AN:

3503

South Asian (SAS)

AF:

0.988

AC:

2476

AN:

2505

European-Finnish (FIN)

AF:

0.980

AC:

5587

AN:

5701

Middle Eastern (MID)

AF:

0.953

AC:

205

AN:

215

European-Non Finnish (NFE)

AF:

0.966

AC:

50939

AN:

52737

Other (OTH)

AF:

0.970

AC:

1446

AN:

1490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

190

285

380

475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.951

Hom.:

3209

Bravo

AF:

0.978

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.92

(source)

DANN

Benign

0.67

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over