10-87961051-T-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000371953.8(PTEN):c.959T>A(p.Leu320Ter) 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. L320L) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000371953.8 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.959T>A | p.Leu320Ter | stop_gained | 8/9 | ENST00000371953.8 | NP_000305.3 | |
PTEN | NM_001304717.5 | c.1478T>A | p.Leu493Ter | stop_gained | 9/10 | NP_001291646.4 | ||
PTEN | NM_001304718.2 | c.368T>A | p.Leu123Ter | stop_gained | 8/9 | NP_001291647.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.959T>A | p.Leu320Ter | stop_gained | 8/9 | 1 | NM_000314.8 | ENSP00000361021 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 36
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Cowden syndrome 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Oct 03, 2023 | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. - |
PTEN hamartoma tumor syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 24, 2020 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). This variant has been reported in an individual affected with clinical features of Cowden syndrome (PMID: 10234502, 31149344). ClinVar contains an entry for this variant (Variation ID: 575793). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu320*) in the PTEN gene. It is expected to result in an absent or disrupted protein product. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 31, 2023 | The c.959T>A (p.L320*) alteration, located in exon 8 (coding exon 8) of the PTEN gene, consists of a T to A substitution at nucleotide position 959. This changes the amino acid from a leucine (L) to a stop codon at amino acid position 320. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been identified in multiple individuals with features consistent with PTEN hamartoma tumor syndrome (Piccione, 2013; Vanderver, 2014; Eng, 2003). Based on the available evidence, this alteration is classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at