rs45517137
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001406689.1(TSC2):c.-561C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
TSC2
NM_001406689.1 5_prime_UTR_premature_start_codon_gain
NM_001406689.1 5_prime_UTR_premature_start_codon_gain
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 0.388
Genes affected
TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. 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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2024 | The p.L291M variant (also known as c.871C>A), located in coding exon 9 of the TSC2 gene, results from a C to A substitution at nucleotide position 871. The leucine at codon 291 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.;.;.;.;.;.;.;.;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;M;M;.;.;.;M;.;M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;N;.;N;.;.;N;N;.;.;.;.;N
REVEL
Uncertain
Sift
Pathogenic
D;.;.;D;.;D;.;.;D;D;.;.;.;.;D
Sift4G
Pathogenic
D;.;.;D;.;D;.;.;D;D;.;.;.;.;D
Polyphen
D;.;.;.;D;D;.;.;D;D;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);.;Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);.;Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);Gain of catalytic residue at L291 (P = 0.0028);.;
MVP
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.