6-170561925-ACAGCAGCAGCAGCAG-ACAGCAGCAGCAG

Variant names:

• chr6-170561925-ACAG-A
• rs113202486
• NM_003194.5:c.213_215delGCA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_003194.5(TBP):​c.213_215delGCA​(p.Gln72del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 981,272 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: TBP NM_003194.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00

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.

• BP6: Variant 6-170561925-ACAG-A is Benign according to our data. Variant chr6-170561925-ACAG-A is described in Lovd as [Benign]. Variant chr6-170561925-ACAG-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBP	NM_003194.5	c.213_215delGCA	p.Gln72del	disruptive_inframe_deletion	Exon 3 of 8	ENST00000392092.7	NP_003185.1
TBP	NM_001172085.2	c.153_155delGCA	p.Gln52del	disruptive_inframe_deletion	Exon 2 of 7		NP_001165556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBP	ENST00000392092.7	c.213_215delGCA	p.Gln72del	disruptive_inframe_deletion	Exon 3 of 8	1	NM_003194.5	ENSP00000375942.2

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 185 AN: 127366 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000423

Gnomad ASJ AF: 0.000315

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.00161

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000408

Gnomad OTH AF: 0.00247

GnomAD4 exome AF: 0.00119 AC: 1019 AN: 853810 Hom.: 2 AF XY: 0.00110 AC XY: 488 AN XY: 442598

Gnomad4 AFR exome AF: 0.00522

Gnomad4 AMR exome AF: 0.000691

Gnomad4 ASJ exome AF: 0.00116

Gnomad4 EAS exome AF: 0.00745

Gnomad4 SAS exome AF: 0.000864

Gnomad4 FIN exome AF: 0.000756

Gnomad4 NFE exome AF: 0.000790

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00147 AC: 187 AN: 127462 Hom.: 0 Cov.: 0 AF XY: 0.00147 AC XY: 89 AN XY: 60416

Gnomad4 AFR AF: 0.00334

Gnomad4 AMR AF: 0.000422

Gnomad4 ASJ AF: 0.000315

Gnomad4 EAS AF: 0.00812

Gnomad4 SAS AF: 0.00161

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.000408

Gnomad4 OTH AF: 0.00244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs113202486; hg19: chr6-170871013;