rs201334685
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_000548.5(TSC2):āc.1613C>Gā(p.Ser538Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,756 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. S538F) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSC2 | NM_000548.5 | c.1613C>G | p.Ser538Cys | missense_variant | 16/42 | ENST00000219476.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC2 | ENST00000219476.9 | c.1613C>G | p.Ser538Cys | missense_variant | 16/42 | 5 | NM_000548.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250236Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135334
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461500Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727026
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74464
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 25, 2022 | The p.S538C variant (also known as c.1613C>G), located in coding exon 15 of the TSC2 gene, results from a C to G substitution at nucleotide position 1613. The serine at codon 538 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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 20, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at