rs45517136
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 4P and 7B. PM1PM5BP4_ModerateBP6BS2
The NM_000548.5(TSC2):āc.857T>Cā(p.Met286Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,583,092 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M286V) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.857T>C | p.Met286Thr | missense_variant | 10/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.857T>C | p.Met286Thr | missense_variant | 10/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000996 AC: 2AN: 200844Hom.: 0 AF XY: 0.00000931 AC XY: 1AN XY: 107414
GnomAD4 exome AF: 0.0000140 AC: 20AN: 1430898Hom.: 0 Cov.: 32 AF XY: 0.0000113 AC XY: 8AN XY: 708656
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 25, 2015 | 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Tuberous sclerosis syndrome Other:1
not provided, no classification provided | curation | Tuberous sclerosis database (TSC2) | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at