9-132911500-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_000368.5(TSC1):c.982C>A(p.Gln328Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q328Q) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Consequence
TSC1
NM_000368.5 missense
NM_000368.5 missense
Scores
2
9
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.17
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;
PP2
?
Missense variant where missense usually causes diseases, TSC1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC1 | NM_000368.5 | c.982C>A | p.Gln328Lys | missense_variant | 10/23 | ENST00000298552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.982C>A | p.Gln328Lys | missense_variant | 10/23 | 1 | NM_000368.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T;.;T;.;T;.;T;.;.;.;.;.;.;.;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M;.;M;.;M;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N
REVEL
Uncertain
Sift
Benign
T;T;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T
Sift4G
Benign
T;T;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T
Polyphen
B;.;B;.;B;.;B;.;.;.;.;P;P;P;.;.;.;B
Vest4
MutPred
Gain of methylation at Q328 (P = 0.0052);.;Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);.;.;Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);Gain of methylation at Q328 (P = 0.0052);.;Gain of methylation at Q328 (P = 0.0052);
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.