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Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3

The NM_003194.5(TBP):​c.261_281dupGCAGCAGCAGCAGCAGCAGCA​(p.Gln88_Gln94dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,405,074 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 24)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

TBP
NM_003194.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.290
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_003194.5

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TBPNM_003194.5 linkc.261_281dupGCAGCAGCAGCAGCAGCAGCA p.Gln88_Gln94dup disruptive_inframe_insertion 3/8 ENST00000392092.7 NP_003185.1 P20226-1Q32MN7
TBPNM_001172085.2 linkc.201_221dupGCAGCAGCAGCAGCAGCAGCA p.Gln68_Gln74dup disruptive_inframe_insertion 2/7 NP_001165556.1 P20226-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TBPENST00000392092.7 linkc.261_281dupGCAGCAGCAGCAGCAGCAGCA p.Gln88_Gln94dup disruptive_inframe_insertion 3/81 NM_003194.5 ENSP00000375942.2 P20226-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
15
AN:
143372
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.000102
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000200
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000141
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000317
AC:
40
AN:
1261702
Hom.:
0
Cov.:
0
AF XY:
0.0000301
AC XY:
19
AN XY:
630696
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000260
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.000151
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000371
GnomAD4 genome
AF:
0.000105
AC:
15
AN:
143372
Hom.:
0
Cov.:
24
AF XY:
0.000143
AC XY:
10
AN XY:
69954
show subpopulations
Gnomad4 AFR
AF:
0.000102
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000200
Gnomad4 NFE
AF:
0.000141
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs752404282; hg19: chr6-170871046; API