NM_000314.8:c.212G>C
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_Strong
The NM_000314.8(PTEN):c.212G>C(p.Cys71Ser) variant causes a missense, splice region 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. 12/21 in silico tools predict a damaging outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. C71Y) has been classified as Pathogenic.
Frequency
Consequence
NM_000314.8 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.212G>C | p.Cys71Ser | missense_variant, splice_region_variant | Exon 4 of 9 | ENST00000371953.8 | NP_000305.3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 29
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Uncertain:1
This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 71 of the PTEN protein (p.Cys71Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on PTEN function (PMID: 24292679, 25504433, 26415504). This variant disrupts the p.Cys71 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been determined to be pathogenic (internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.