6-170561958-ACAGCAGCAG-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_003194.5(TBP):c.273_281del(p.Gln93_Gln95del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000411 in 143,466 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. Q75Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00041 (1 hom., cov: 21)
  • Exomes 𝑓: 0.0052 (451 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBP NM_003194.5 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.47

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_003194.5
• BP6: Variant 6-170561958-ACAGCAGCAG-A is Benign according to our data. Variant chr6-170561958-ACAGCAGCAG-A is described in ClinVar as [Benign]. Clinvar id is 599434.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 195 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBP	NM_003194.5	c.273_281del	p.Gln93_Gln95del	inframe_deletion	3/8	ENST00000392092.7
TBP	NM_001172085.2	c.213_221del	p.Gln73_Gln75del	inframe_deletion	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBP	ENST00000392092.7	c.273_281del	p.Gln93_Gln95del	inframe_deletion	3/8	1	NM_003194.5	P2

Frequencies

GnomAD3 genomes AF: 0.000419 AC: 60 AN: 143360 Hom.: 1 Cov.: 21

Gnomad AFR AF: 0.000332

Gnomad AMI AF: 0.00123

Gnomad AMR AF: 0.000205

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00203

Gnomad SAS AF: 0.000864

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000392

Gnomad OTH AF: 0.00202

GnomAD3 exomes AF: 0.00968 AC: 1449 AN: 149640 Hom.: 195 AF XY: 0.0106 AC XY: 862 AN XY: 81604

Gnomad AFR exome AF: 0.00470

Gnomad AMR exome AF: 0.00733

Gnomad ASJ exome AF: 0.00341

Gnomad EAS exome AF: 0.0188

Gnomad SAS exome AF: 0.00653

Gnomad FIN exome AF: 0.00726

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00680

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00521 AC: 6567 AN: 1259378 Hom.: 451 AF XY: 0.00482 AC XY: 3036 AN XY: 629606

Gnomad4 AFR exome AF: 0.00139

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.00302

Gnomad4 SAS exome AF: 0.00241

Gnomad4 FIN exome AF: 0.00170

Gnomad4 NFE exome AF: 0.00612

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.000411 AC: 59 AN: 143466 Hom.: 1 Cov.: 21 AF XY: 0.000385 AC XY: 27 AN XY: 70060

Gnomad4 AFR AF: 0.000331

Gnomad4 AMR AF: 0.000205

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00203

Gnomad4 SAS AF: 0.000864

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000392

Gnomad4 OTH AF: 0.00150

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

Mar 20, 2017

Normal variation in repetative sequence -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs752404282; hg19: chr6-170871046;