NM_003194.5:c.216A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_003194.5(TBP):c.216A>G(p.Gln72Gln) variant causes a synonymous 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. QQ72Q?) has been classified as Benign.

Frequency

Genomes: 𝑓 0.43 ( 396 hom., cov: 0)

Exomes 𝑓: 0.22 ( 2037 hom. )

Failed GnomAD Quality Control

Consequence

TBP
NM_003194.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0240

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 6-170561952-A-G is Benign according to our data. Variant chr6-170561952-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 130558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-170561952-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.024 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBP	NM_003194.5 link	c.216A>G	p.Gln72Gln	synonymous_variant	Exon 3 of 8	ENST00000392092.7	NP_003185.1	P20226-1Q32MN7
TBP	NM_001172085.2 link	c.156A>G	p.Gln52Gln	synonymous_variant	Exon 2 of 7		NP_001165556.1	P20226-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBP	ENST00000392092.7 link	c.216A>G	p.Gln72Gln	synonymous_variant	Exon 3 of 8	1	NM_003194.5	ENSP00000375942.2		P20226-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

9072

AN:

21320

Hom.:

397

Cov.:

FAILED QC

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.405

GnomAD3 exomes

AF:

0.0256

AC:

3139

AN:

122506

Hom.:

AF XY:

0.0246

AC XY:

1610

AN XY:

65532

show subpopulations

Gnomad AFR exome

AF:

0.0174

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0205

Gnomad EAS exome

AF:

0.00141

Gnomad SAS exome

AF:

0.00922

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0382

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.221

AC:

40358

AN:

182754

Hom.:

2037

Cov.:

AF XY:

0.227

AC XY:

20689

AN XY:

91106

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.140

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.426

AC:

9067

AN:

21308

Hom.:

396

Cov.:

AF XY:

0.421

AC XY:

4229

AN XY:

10042

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.420

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.435

Gnomad4 OTH

AF:

0.408

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 17

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jun 27, 2014

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Nov 09, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.4

DANN

Benign

0.17

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