6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAG

Position:

• chr6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_003194.5(TBP):​c.264_281delGCAGCAGCAGCAGCAGCA​(p.Gln89_Gln94del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00113 in 1,405,090 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0011 (6 hom.)
• Consequence: TBP NM_003194.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• 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 -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_003194.5
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBP	NM_003194.5	c.264_281delGCAGCAGCAGCAGCAGCA	p.Gln89_Gln94del	disruptive_inframe_deletion	3/8	ENST00000392092.7	NP_003185.1
TBP	NM_001172085.2	c.204_221delGCAGCAGCAGCAGCAGCA	p.Gln69_Gln74del	disruptive_inframe_deletion	2/7		NP_001165556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBP	ENST00000392092.7	c.264_281delGCAGCAGCAGCAGCAGCA	p.Gln89_Gln94del	disruptive_inframe_deletion	3/8	1	NM_003194.5	ENSP00000375942.2

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 188 AN: 143354 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000716

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000956

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000400

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00218

Gnomad OTH AF: 0.00101

GnomAD4 exome AF: 0.00111 AC: 1401 AN: 1261630 Hom.: 6 AF XY: 0.00107 AC XY: 674 AN XY: 630648

Gnomad4 AFR exome AF: 0.000765

Gnomad4 AMR exome AF: 0.000406

Gnomad4 ASJ exome AF: 0.0000843

Gnomad4 EAS exome AF: 0.000104

Gnomad4 SAS exome AF: 0.000147

Gnomad4 FIN exome AF: 0.000559

Gnomad4 NFE exome AF: 0.00133

Gnomad4 OTH exome AF: 0.00121

GnomAD4 genome AF: 0.00132 AC: 189 AN: 143460 Hom.: 0 Cov.: 21 AF XY: 0.00106 AC XY: 74 AN XY: 70060

Gnomad4 AFR AF: 0.000739

Gnomad4 AMR AF: 0.000955

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000203

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000400

Gnomad4 NFE AF: 0.00218

Gnomad4 OTH AF: 0.00100

ClinVar

Not reported in ClinVar

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;