NM_000314.8:c.1026G>T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate
The NM_000314.8(PTEN):c.1026G>T(p.Lys342Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_000314.8 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.1026G>T | p.Lys342Asn | missense_variant, splice_region_variant | Exon 8 of 9 | ENST00000371953.8 | NP_000305.3 | |
PTEN | NM_001304717.5 | c.1545G>T | p.Lys515Asn | missense_variant, splice_region_variant | Exon 9 of 10 | NP_001291646.4 | ||
PTEN | NM_001304718.2 | c.435G>T | p.Lys145Asn | missense_variant, splice_region_variant | Exon 8 of 9 | NP_001291647.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 36
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Pathogenic:1
ClinVar contains an entry for this variant (Variation ID: 1067478). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on PTEN function (PMID: 10866302). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This missense change has been observed in individual(s) with unspecified thyroid lesion (follicular lesion of undetermined significance) and breast fibroadenoma (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 342 of the PTEN protein (p.Lys342Asn). This variant also falls at the last nucleotide of exon 8, which is part of the consensus splice site for this exon. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.