16-2081763-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_000548.5(TSC2):c.3779C>T(p.Thr1260Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,626 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. T1260A) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.3779C>T | p.Thr1260Met | missense_variant | 31/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.3779C>T | p.Thr1260Met | missense_variant | 31/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249928Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135650
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1460398Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726508
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74384
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | 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. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 07, 2021 | - - |
Tuberous sclerosis 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 04, 2019 | This variant is associated with the following publications: (PMID: 31856217) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at