Variant 6-170561966-AG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1BP6_ModerateBA1

The NM_003194.5(TBP):c.231del(p.Gln77HisfsTer67) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 1,036,150 control chromosomes in the GnomAD database, including 3,499 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. Q77Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.14 ( 1707 hom., cov: 27)

Exomes 𝑓: 0.086 ( 1792 hom. )

Consequence

TBP
NM_003194.5 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.39

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 6-170561966-AG-A is Benign according to our data. Variant chr6-170561966-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 3065444.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-170561966-AG-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBP	NM_003194.5 linkuse as main transcript	c.231del	p.Gln77HisfsTer67	frameshift_variant	3/8	ENST00000392092.7	NP_003185.1
TBP	NM_001172085.2 linkuse as main transcript	c.171del	p.Gln57HisfsTer67	frameshift_variant	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.231del	p.Gln77HisfsTer67	frameshift_variant	3/8	1	NM_003194.5	ENSP00000375942	P2	P20226-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

19073

AN:

139944

Hom.:

1705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0913

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0590

Gnomad MID

AF:

0.129

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.146

GnomAD4 exome

AF:

0.0863

AC:

77293

AN:

896102

Hom.:

1792

Cov.:

AF XY:

0.0931

AC XY:

41824

AN XY:

449306

show subpopulations

Gnomad4 AFR exome

AF:

0.0581

Gnomad4 AMR exome

AF:

0.122

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.447

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.0695

Gnomad4 NFE exome

AF:

0.0592

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.136

AC:

19091

AN:

140048

Hom.:

1707

Cov.:

AF XY:

0.132

AC XY:

8978

AN XY:

68012

show subpopulations

Gnomad4 AFR

AF:

0.0914

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.492

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.0590

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.0466

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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