9-132911475-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000368.5(TSC1):c.1007G>C(p.Arg336Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R336Q) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Consequence
TSC1
NM_000368.5 missense
NM_000368.5 missense
Scores
3
7
9
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.57
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TSC1 | ENST00000298552.9 | c.1007G>C | p.Arg336Pro | missense_variant | 10/23 | 1 | NM_000368.5 | ENSP00000298552.3 | ||
| TSC1 | ENST00000490179.4 | c.1007G>C | p.Arg336Pro | missense_variant | 11/24 | 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;.;T;.;T;.;T;.;.;.;.;.;.;.;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;.;.;.;D;D;.;D;.;.;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;.;L;.;L;.;.;.;.;.;.;.;.;.;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N
REVEL
Uncertain
Sift
Benign
D;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D
Sift4G
Benign
T;T;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T
Polyphen
B;.;B;.;B;.;B;.;.;.;.;B;B;B;.;.;.;P
Vest4
MutPred
Gain of glycosylation at R336 (P = 0.0238);.;Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);.;.;Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);Gain of glycosylation at R336 (P = 0.0238);.;Gain of glycosylation at R336 (P = 0.0238);
MVP
MPC
ClinPred
D
GERP RS
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.