rs367601694
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000368.5(TSC1):c.1141+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,611,372 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000021 ( 2 hom. )
Consequence
TSC1
NM_000368.5 intron
NM_000368.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.496
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 9-132910992-A-G is Benign according to our data. Variant chr9-132910992-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 466008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132910992-A-G is described in Lovd as [Likely_benign]. Variant chr9-132910992-A-G is described in Lovd as [Benign].
BS2
?
High AC in GnomAdExome4 at 30 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC1 | NM_000368.5 | c.1141+10T>C | intron_variant | ENST00000298552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.1141+10T>C | intron_variant | 1 | NM_000368.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251150Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135712
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GnomAD4 exome AF: 0.0000206 AC: 30AN: 1459028Hom.: 2 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 726086
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152344Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74504
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Tuberous sclerosis 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 02, 2020 | - - |
TSC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 01, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at