rs1060500116
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000314.8(PTEN):c.176C>A(p.Ser59Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S59S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000314.8 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.176C>A | p.Ser59Ter | stop_gained | 3/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.695C>A | p.Ser232Ter | stop_gained | 4/10 | ||
PTEN | NM_001304718.2 | c.-540-5522C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.176C>A | p.Ser59Ter | stop_gained | 3/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1438174Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 716300
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 04, 2022 | This sequence change creates a premature translational stop signal (p.Ser59*) in the PTEN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Cowden syndrome (PMID: 21194675, 30482242, 30809968). ClinVar contains an entry for this variant (Variation ID: 847797). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 19, 2020 | The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at