10-87933222-T-C
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_000314.8(PTEN):c.463T>C(p.Tyr155His) 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. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y155C) has been classified as Pathogenic.
Frequency
Consequence
NM_000314.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.463T>C | p.Tyr155His | missense_variant | 5/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.982T>C | p.Tyr328His | missense_variant | 6/10 | ||
PTEN | NM_001304718.2 | c.-288T>C | 5_prime_UTR_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.463T>C | p.Tyr155His | 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
Cowden syndrome 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Sep 28, 2023 | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 32350270]. This variant is expected to disrupt protein structure [Myriad internal data]. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2013 | ​The p.Y155H variant (also known as c.463T>C) is located in coding exon 5 of the PTEN gene. This alteration results from a T to C substitution at nucleotide position 463. The tyrosine at codon 155 is replaced by histidine, an amino acid with similar properties. This alteration has been reported in the literature in multiple patients who met the clinical criteria for Cowden Syndrome (Tan et al. Am J Hum Genet. 2011 Jan 7;88(1):42-56; Pilarski et al. J Med Genet. 2011 Aug;48(8):505-12). This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. - |
Macrocephaly-autism syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Mar 14, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at