9-132891987-G-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000368.5(TSC1):c.*4248C>A variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TSC1
NM_000368.5 3_prime_UTR
NM_000368.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.00
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 was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TSC1 | ENST00000298552.9 | c.*4248C>A | 3_prime_UTR_variant | Exon 23 of 23 | 1 | NM_000368.5 | ENSP00000298552.3 | |||
| TSC1 | ENST00000490179.4 | c.*4248C>A | 3_prime_UTR_variant | Exon 24 of 24 | 3 | ENSP00000495533.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 80824Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 37136
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
80824
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
37136
African (AFR)
AF:
AC:
0
AN:
3886
American (AMR)
AF:
AC:
0
AN:
2498
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
5104
East Asian (EAS)
AF:
AC:
0
AN:
11370
South Asian (SAS)
AF:
AC:
0
AN:
698
European-Finnish (FIN)
AF:
AC:
0
AN:
96
Middle Eastern (MID)
AF:
AC:
0
AN:
492
European-Non Finnish (NFE)
AF:
AC:
0
AN:
49928
Other (OTH)
AF:
AC:
0
AN:
6752
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Tuberous sclerosis syndrome Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Isolated focal cortical dysplasia type II Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
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