rs1060503216
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000368.5(TSC1):c.1138A>T(p.Thr380Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Consequence
TSC1
NM_000368.5 missense
NM_000368.5 missense
Scores
1
18
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.43
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05797714).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TSC1 | ENST00000298552.9 | c.1138A>T | p.Thr380Ser | missense_variant | Exon 11 of 23 | 1 | NM_000368.5 | ENSP00000298552.3 | ||
| TSC1 | ENST00000490179.4 | c.1138A>T | p.Thr380Ser | missense_variant | Exon 12 of 24 | 3 | ENSP00000495533.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
T;.;T;.;T;.;T;.;.;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T;T;T;.;.;.;T;T;.;.;.;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;.;N;.;N;.;.;.;.;.;.;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.;.;.;.;.;.;.;.;.;.;.;.
REVEL
Benign
Sift
Benign
T;T;T;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G
Benign
T;T;T;.;.;.;.;.;.;.;.;.;.;.;.
Polyphen
B;.;B;.;B;.;B;.;.;.;B;B;B;.;.
Vest4
MutPred
Loss of glycosylation at T379 (P = 0.0921);.;Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);.;Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);Loss of glycosylation at T379 (P = 0.0921);.;
MVP
MPC
ClinPred
T
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.