Variant 6-170561958-A-ACAGCAGCAGCAGCAGCAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP5_ModerateBP3

The NM_003194.5(TBP):c.264_281dup(p.Gln90_Gln95dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,405,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q74Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

TBP
NM_003194.5 inframe_insertion

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 0.290

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 6-170561958-A-ACAGCAGCAGCAGCAGCAG is Pathogenic according to our data. Variant chr6-170561958-A-ACAGCAGCAGCAGCAGCAG is described in ClinVar as [Pathogenic]. Clinvar id is 2576597.Status of the report is criteria_provided_single_submitter, 1 stars.

BP3

Nonframeshift variant in repetitive region in NM_003194.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBP	NM_003194.5 linkuse as main transcript	c.264_281dup	p.Gln90_Gln95dup	inframe_insertion	3/8	ENST00000392092.7	NP_003185.1
TBP	NM_001172085.2 linkuse as main transcript	c.204_221dup	p.Gln70_Gln75dup	inframe_insertion	2/7		NP_001165556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBP	ENST00000392092.7 linkuse as main transcript	c.264_281dup	p.Gln90_Gln95dup	inframe_insertion	3/8	1	NM_003194.5	ENSP00000375942	P2	P20226-1

Frequencies

GnomAD3 genomes

AF:

0.000181

AC:

AN:

143372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000204

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.000313

Gnomad EAS

AF:

0.000203

Gnomad SAS

AF:

0.000432

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000761

AC:

AN:

1261698

Hom.:

Cov.:

AF XY:

0.0000904

AC XY:

AN XY:

630694

show subpopulations

Gnomad4 AFR exome

AF:

0.0000348

Gnomad4 AMR exome

AF:

0.000215

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000208

Gnomad4 SAS exome

AF:

0.000196

Gnomad4 FIN exome

AF:

0.0000215

Gnomad4 NFE exome

AF:

0.0000531

Gnomad4 OTH exome

AF:

0.000204

GnomAD4 genome

AF:

0.000181

AC:

AN:

143478

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

AN XY:

70064

show subpopulations

Gnomad4 AFR

AF:

0.000204

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.000313

Gnomad4 EAS

AF:

0.000203

Gnomad4 SAS

AF:

0.000432

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 17

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

May 24, 2023

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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