rs786204903
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000314.8(PTEN):c.758_761delTCAA(p.Ile253LysfsTer2) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000314.8 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.758_761delTCAA | p.Ile253LysfsTer2 | frameshift_variant | Exon 7 of 9 | ENST00000371953.8 | NP_000305.3 | |
PTEN | NM_001304717.5 | c.1277_1280delTCAA | p.Ile426LysfsTer2 | frameshift_variant | Exon 8 of 10 | NP_001291646.4 | ||
PTEN | NM_001304718.2 | c.167_170delTCAA | p.Ile56LysfsTer2 | frameshift_variant | Exon 7 of 9 | NP_001291647.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Pathogenic:1
This sequence change deletes 4 nucleotides from exon 7 of the PTEN mRNA (c.758_761delTCAA), causing a frameshift at codon 253. This creates a premature translational stop signal (p.Ile253Lysfs*2) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). For these reasons, this variant has been classified as Pathogenic. -
Hereditary cancer-predisposing syndrome Pathogenic:1
This variant is denoted c.758_761delTCAA at the cDNA level and p.I253KfsX2 at the protein level. The normal sequence with the bases that are deleted in braces is: GATA{TCAA}AGTA. The c.758_761delTCAA mutation in the PTEN gene causes a frameshift starting with codon Isoleucine 253, changes this amino acid to a Lysine residue and creates a premature Stop codon at position 2 of the newreading frame, denoted p.Ile253LysfsX2. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in PTEN panel(s). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at