9-132912398-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000368.5(TSC1):c.797C>A(p.Pro266His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Consequence
TSC1
NM_000368.5 missense
NM_000368.5 missense
Scores
8
9
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 10.0
Genes affected
TSC1 (HGNC:12362): (TSC complex subunit 1) This gene is a tumor suppressor gene that encodes the growth inhibitory protein hamartin. The encoded protein interacts with and stabilizes the GTPase activating protein tuberin. This hamartin-tuberin complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. This protein also functions as a co-chaperone for Hsp90 that inhibits its ATPase activity. This protein functions as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients, including TSC2 and thereby preventing their ubiquitination and proteasomal degradation. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.837
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TSC1 | ENST00000298552.9 | c.797C>A | p.Pro266His | missense_variant | 9/23 | 1 | NM_000368.5 | ENSP00000298552.3 | ||
| TSC1 | ENST00000490179.4 | c.797C>A | p.Pro266His | missense_variant | 10/24 | 3 | ENSP00000495533.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D;.;D;.;D;.;.;.;.;.;.;.;.;.;.;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;.;.;.;D;D;.;D;.;.;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M;.;M;.;M;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.
Sift4G
Pathogenic
D;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.
Polyphen
D;.;D;.;D;.;D;.;.;.;.;D;D;D;.;.;.;D;.
Vest4
MutPred
Loss of glycosylation at T267 (P = 0.1286);.;Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);.;.;Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);Loss of glycosylation at T267 (P = 0.1286);.;Loss of glycosylation at T267 (P = 0.1286);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.