chr6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAG-A

Position:

• chr6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAG-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_003194.5(TBP):​c.258_281del​(p.Gln88_Gln95del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000154 in 1,405,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00033 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: TBP NM_003194.5 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.03

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 Likely_benign. Variant got -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_003194.5
• BP6: Variant 6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAG-A is Benign according to our data. Variant chr6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAG-A is described in ClinVar as [Benign]. Clinvar id is 2657159.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBP	NM_003194.5	c.258_281del	p.Gln88_Gln95del	inframe_deletion	3/8	ENST00000392092.7	NP_003185.1
TBP	NM_001172085.2	c.198_221del	p.Gln68_Gln75del	inframe_deletion	2/7		NP_001165556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBP	ENST00000392092.7	c.258_281del	p.Gln88_Gln95del	inframe_deletion	3/8	1	NM_003194.5	ENSP00000375942	P2

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 48 AN: 143368 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00178

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000432

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000173

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000133 AC: 168 AN: 1261690 Hom.: 0 AF XY: 0.000127 AC XY: 80 AN XY: 630690

Gnomad4 AFR exome AF: 0.000139

Gnomad4 AMR exome AF: 0.000716

Gnomad4 ASJ exome AF: 0.000126

Gnomad4 EAS exome AF: 0.0000521

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.0000215

Gnomad4 NFE exome AF: 0.000122

Gnomad4 OTH exome AF: 0.000223

GnomAD4 genome AF: 0.000335 AC: 48 AN: 143474 Hom.: 0 Cov.: 21 AF XY: 0.000400 AC XY: 28 AN XY: 70062

Gnomad4 AFR AF: 0.000229

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000432

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000173

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

TBP: BS1, BS2 -

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;