6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_003194.5(TBP):c.276_281dupGCAGCA(p.Gln93_Gln94dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,404,802 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 2 hom., cov: 24)

Exomes 𝑓: 0.0048 ( 19 hom. )

Consequence

TBP
NM_003194.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.290

Publications

4 publications found

Variant links:

Genes affected

TBP (HGNC:11588): (TATA-box binding protein) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (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 TBP, the TATA-binding protein. A distinctive feature of TBP is a long string of glutamines in the N-terminus. This region of the protein modulates the DNA binding activity of the C terminus, and modulation of DNA binding affects the rate of transcription complex formation and initiation of transcription. The number of CAG repeats encoding the polyglutamine tract is usually 25-42, and expansion of the number of repeats to 45-66 increases the length of the polyglutamine string and is associated with spinocerebellar ataxia 17, a neurodegenerative disorder classified as a polyglutamine disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2016]

TBP Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 17
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

TBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_003194.5

BP6

Variant 6-170561958-A-ACAGCAG is Benign according to our data. Variant chr6-170561958-A-ACAGCAG is described in ClinVar as Likely_benign. ClinVar VariationId is 445790.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 601 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003194.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBP	NM_003194.5	MANE Select	c.276_281dupGCAGCA	p.Gln93_Gln94dup	disruptive_inframe_insertion	Exon 3 of 8	NP_003185.1
	TBP	NM_001172085.2		c.216_221dupGCAGCA	p.Gln73_Gln74dup	disruptive_inframe_insertion	Exon 2 of 7	NP_001165556.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TBP	ENST00000392092.7	TSL:1 MANE Select	c.276_281dupGCAGCA	p.Gln93_Gln94dup	disruptive_inframe_insertion	Exon 3 of 8	ENSP00000375942.2
TBP	ENST00000230354.10	TSL:1	c.276_281dupGCAGCA	p.Gln93_Gln94dup	disruptive_inframe_insertion	Exon 3 of 8	ENSP00000230354.5
TBP	ENST00000421512.5	TSL:1	c.276_281dupGCAGCA	p.Gln93_Gln94dup	disruptive_inframe_insertion	Exon 3 of 5	ENSP00000400008.1

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

600

AN:

143368

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00394

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00355

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00852

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.000901

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00436

Gnomad OTH

AF:

0.00253

GnomAD2 exomes

AF:

0.00435

AC:

651

AN:

149640

AF XY:

0.00440

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.000594

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00207

GnomAD4 exome

AF:

0.00476

AC:

6009

AN:

1261328

Hom.:

Cov.:

AF XY:

0.00496

AC XY:

3129

AN XY:

630480

show subpopulations

African (AFR)

AF:

0.00372

AC:

107

AN:

28774

American (AMR)

AF:

0.00341

AC:

143

AN:

41886

Ashkenazi Jewish (ASJ)

AF:

0.000506

AC:

AN:

23728

East Asian (EAS)

AF:

0.00604

AC:

232

AN:

38388

South Asian (SAS)

AF:

0.0104

AC:

847

AN:

81662

European-Finnish (FIN)

AF:

0.00105

AC:

AN:

46474

Middle Eastern (MID)

AF:

0.00384

AC:

AN:

4954

European-Non Finnish (NFE)

AF:

0.00458

AC:

4309

AN:

941574

Other (OTH)

AF:

0.00540

AC:

291

AN:

53888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.609

Heterozygous variant carriers

180

360

541

721

901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

162

324

486

648

810

<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

AF:

0.00419

AC:

601

AN:

143474

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

271

AN XY:

70062

show subpopulations

African (AFR)

AF:

0.00392

AC:

154

AN:

39242

American (AMR)

AF:

0.00355

AC:

AN:

14660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3200

East Asian (EAS)

AF:

0.00854

AC:

AN:

4916

South Asian (SAS)

AF:

0.0130

AC:

AN:

4626

European-Finnish (FIN)

AF:

0.000901

AC:

AN:

9992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00436

AC:

278

AN:

63756

Other (OTH)

AF:

0.00300

AC:

AN:

1998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.576

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00148

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.29

Mutation Taster

=54/46

polymorphism

(source)

Splicing

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

Publications

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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