chr16-2062525-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6
The NM_000548.5(TSC2):āc.1286A>Gā(p.Tyr429Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. Y429F) has been classified as Uncertain significance.
Frequency
Consequence
NM_000548.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.1286A>G | p.Tyr429Cys | missense_variant | 13/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.1286A>G | p.Tyr429Cys | missense_variant | 13/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247350Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133926
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459900Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725952
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74506
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TSC2: PM2 - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 09, 2023 | The p.Y429C variant (also known as c.1286A>G), located in coding exon 12 of the TSC2 gene, results from an A to G substitution at nucleotide position 1286. The tyrosine at codon 429 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Tuberous sclerosis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at