NM_003194.5:c.210_215delGCAGCA

Variant names:

• chr6-170561925-ACAGCAG-A
• rs113202486
• NM_003194.5:c.210_215delGCAGCA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_003194.5(TBP):​c.210_215delGCAGCA​(p.Gln71_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 0.000659 in 981,386 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q70Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00069 (1 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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBP	NM_003194.5	c.210_215delGCAGCA	p.Gln71_Gln72del	disruptive_inframe_deletion	Exon 3 of 8	ENST00000392092.7	NP_003185.1
TBP	NM_001172085.2	c.150_155delGCAGCA	p.Gln51_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.210_215delGCAGCA	p.Gln71_Gln72del	disruptive_inframe_deletion	Exon 3 of 8	1	NM_003194.5	ENSP00000375942.2

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 56 AN: 127366 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000338

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00319

Gnomad SAS AF: 0.00385

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000359

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000692 AC: 591 AN: 853926 Hom.: 1 AF XY: 0.000752 AC XY: 333 AN XY: 442654

Gnomad4 AFR exome AF: 0.0000527

Gnomad4 AMR exome AF: 0.000159

Gnomad4 ASJ exome AF: 0.0000462

Gnomad4 EAS exome AF: 0.00269

Gnomad4 SAS exome AF: 0.00250

Gnomad4 FIN exome AF: 0.0000473

Gnomad4 NFE exome AF: 0.000488

Gnomad4 OTH exome AF: 0.000780

GnomAD4 genome AF: 0.000439 AC: 56 AN: 127460 Hom.: 0 Cov.: 0 AF XY: 0.000480 AC XY: 29 AN XY: 60416

Gnomad4 AFR AF: 0.000150

Gnomad4 AMR AF: 0.000338

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00320

Gnomad4 SAS AF: 0.00386

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000359

Gnomad4 OTH AF: 0.00

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: rs113202486; hg19: chr6-170871013;