rs9651492
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_000314.8(PTEN):c.457G>A(p.Asp153Asn) variant causes a missense 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D153E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000314.8 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.457G>A | p.Asp153Asn | missense_variant | 5/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.976G>A | p.Asp326Asn | missense_variant | 6/10 | ||
PTEN | NM_001304718.2 | c.-294G>A | 5_prime_UTR_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.457G>A | p.Asp153Asn | missense_variant | 5/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2016 | This sequence change replaces aspartic acid with asparagine at codon 153 of the PTEN protein (p.Asp153Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. In summary, this variant is a rare missense change that is not predicted to affect protein function. While it is absent from the population database and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant has been reported in the literature in individuals affected with breast cancer and it is unclear if this variant was also observed in unaffected control individuals (PMID: 22320991). This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at