6-170561952-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003194.5(TBP):​c.216A>T​(p.Gln72His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q72Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 0)

Consequence

TBP
NM_003194.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0240
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.12873545).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TBPNM_003194.5 linkc.216A>T p.Gln72His missense_variant 3/8 ENST00000392092.7 NP_003185.1 P20226-1Q32MN7
TBPNM_001172085.2 linkc.156A>T p.Gln52His missense_variant 2/7 NP_001165556.1 P20226-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TBPENST00000392092.7 linkc.216A>T p.Gln72His missense_variant 3/81 NM_003194.5 ENSP00000375942.2 P20226-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
8.6
DANN
Benign
0.32
DEOGEN2
Benign
0.35
.;.;T;T;.
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.79
T;T;T;.;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.13
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.34
.;.;N;N;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
0.19
N;N;N;N;N
REVEL
Benign
0.12
Sift
Benign
0.12
T;T;T;T;D
Sift4G
Benign
0.11
T;T;T;T;D
Polyphen
0.68
.;.;P;P;.
Vest4
0.23, 0.20, 0.22
MutPred
0.35
Loss of solvent accessibility (P = 0.4653);.;Loss of solvent accessibility (P = 0.4653);Loss of solvent accessibility (P = 0.4653);Loss of solvent accessibility (P = 0.4653);
MVP
0.34
MPC
0.12
ClinPred
0.38
T
GERP RS
-1.3
Varity_R
0.13
gMVP
0.70

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

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

Other links and lift over

dbSNP: rs55736770; hg19: chr6-170871040; API