chr16-2048050-G-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000548.5(TSC2):c.-45G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,424,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
TSC2
NM_000548.5 5_prime_UTR
NM_000548.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.244
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BP6
?
Variant 16-2048050-G-T is Benign according to our data. Variant chr16-2048050-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 506728.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.-45G>T | 5_prime_UTR_variant | 1/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.-45G>T | 5_prime_UTR_variant | 1/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152162Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000233 AC: 296AN: 1272582Hom.: 0 Cov.: 31 AF XY: 0.000220 AC XY: 136AN XY: 618756
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 18, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Benign
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at