chr6-170561925-A-ACAGCAGCAG

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.207_215dupGCAGCAGCA(p.Gln70_Gln72dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 981,328 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q72Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00069 ( 17 hom. )

Consequence

TBP
NM_003194.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.40

Publications

5 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: Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics

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 6-170561925-A-ACAGCAGCAG is Benign according to our data. Variant chr6-170561925-A-ACAGCAGCAG is described in ClinVar as Likely_benign. ClinVar VariationId is 3390327.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 104 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBP	NM_003194.5	MANE Select	c.207_215dupGCAGCAGCA	p.Gln70_Gln72dup	disruptive_inframe_insertion	Exon 3 of 8	NP_003185.1	P20226-1
	TBP	NM_001172085.2		c.147_155dupGCAGCAGCA	p.Gln50_Gln52dup	disruptive_inframe_insertion	Exon 2 of 7	NP_001165556.1	P20226-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBP	ENST00000392092.7	TSL:1 MANE Select	c.207_215dupGCAGCAGCA	p.Gln70_Gln72dup	disruptive_inframe_insertion	Exon 3 of 8	ENSP00000375942.2	P20226-1
TBP	ENST00000230354.10	TSL:1	c.207_215dupGCAGCAGCA	p.Gln70_Gln72dup	disruptive_inframe_insertion	Exon 3 of 8	ENSP00000230354.5	P20226-1
TBP	ENST00000421512.5	TSL:1	c.207_215dupGCAGCAGCA	p.Gln70_Gln72dup	disruptive_inframe_insertion	Exon 3 of 5	ENSP00000400008.1	Q7Z6S5

Frequencies

GnomAD3 genomes

AF:

0.000817

AC:

104

AN:

127362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000181

Gnomad AMI

AF:

0.00122

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000736

Gnomad SAS

AF:

0.000321

Gnomad FIN

AF:

0.000125

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000978

Gnomad OTH

AF:

0.000617

GnomAD4 exome

AF:

0.000687

AC:

587

AN:

853870

Hom.:

Cov.:

AF XY:

0.000718

AC XY:

318

AN XY:

442618

show subpopulations

African (AFR)

AF:

0.000369

AC:

AN:

18962

American (AMR)

AF:

0.000611

AC:

AN:

37642

Ashkenazi Jewish (ASJ)

AF:

0.000277

AC:

AN:

21622

East Asian (EAS)

AF:

0.000438

AC:

AN:

34236

South Asian (SAS)

AF:

0.000103

AC:

AN:

68288

European-Finnish (FIN)

AF:

0.000922

AC:

AN:

42314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3518

European-Non Finnish (NFE)

AF:

0.000788

AC:

463

AN:

587528

Other (OTH)

AF:

0.000679

AC:

AN:

39760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000816

AC:

104

AN:

127458

Hom.:

Cov.:

AF XY:

0.000944

AC XY:

AN XY:

60412

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33254

American (AMR)

AF:

0.00262

AC:

AN:

11842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3176

East Asian (EAS)

AF:

0.000738

AC:

AN:

4066

South Asian (SAS)

AF:

0.000322

AC:

AN:

3110

European-Finnish (FIN)

AF:

0.000125

AC:

AN:

7980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

252

European-Non Finnish (NFE)

AF:

0.000978

AC:

AN:

61322

Other (OTH)

AF:

0.000611

AC:

AN:

1638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

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:

0.00126

Hom.:

ClinVar

ClinVar submissions

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

2.4

Mutation Taster

=60/40

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

Computational scores

Splicing

Publications

Other links and lift over