16-2060723-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000548.5(TSC2):c.1029C>T(p.Thr343=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,810 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T343T) has been classified as Likely benign.
Frequency
Consequence
NM_000548.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.1029C>T | p.Thr343= | synonymous_variant | 11/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.1029C>T | p.Thr343= | synonymous_variant | 11/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251368Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135914
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461810Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727206
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Tuberous sclerosis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2023 | This variant is present in population databases (rs45468201, gnomAD 0.0009%). This sequence change affects codon 343 of the TSC2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TSC2 protein. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 49137). - |
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