rs121909225
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_000314.8(PTEN):c.104T>C(p.Met35Thr) 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 Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M35V) 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.104T>C | p.Met35Thr | missense_variant | 2/9 | ENST00000371953.8 | NP_000305.3 | |
PTEN | NM_001304717.5 | c.623T>C | p.Met208Thr | missense_variant | 3/10 | NP_001291646.4 | ||
PTEN | NM_001304718.2 | c.-602T>C | 5_prime_UTR_variant | 2/9 | NP_001291647.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.104T>C | p.Met35Thr | missense_variant | 2/9 | 1 | NM_000314.8 | ENSP00000361021.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 29
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 26, 2023 | This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID 17526801, 11476841, 32442409, 26468640, 30311380]. This variant is expected to disrupt protein structure [Myriad internal data]. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 06, 2020 | The p.M35T variant (also known as c.104T>C), located in coding exon 2 of the PTEN gene, results from a T to C substitution at nucleotide position 104. The methionine at codon 35 is replaced by threonine, an amino acid with similar properties. This alteration has described in an individual with Proteus syndrome-like (Zhou X et al. Lancet 2001 Jul; 358(9277):210-1). This alteration has also been described in an individual meeting criteria for Cowden syndrome (CS) (Tan MH et al. Am. J. Hum. Genet. 2011 Jan; 88(1):42-56). A similar alteration at this same amino acid position, p.M35V, has also been identified in multiple individuals meeting full or relaxed International Cowden Consortium operational criteria for Cowden syndrome (CS) (Tan et al.; Ambry internal data). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at