chr16-2084620-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_000548.5(TSC2):c.4398G>T(p.Ser1466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,601,388 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). Synonymous variant affecting the same amino acid position (i.e. S1466S) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.4398G>T | p.Ser1466= | synonymous_variant | 34/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.4398G>T | p.Ser1466= | synonymous_variant | 34/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000420 AC: 1AN: 238238Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130694
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1449184Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1AN XY: 721408
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74350
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Benign:2
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 | - - |
Tuberous sclerosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 20, 2023 | This variant is located in the TSC2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has been identified in 5/269612 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2021 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 02, 2016 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at