10-87933166-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001304718.2(PTEN):c.-344G>T variant causes a 5 prime UTR premature start codon gain 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 Pathogenic (★).
Frequency
Consequence
NM_001304718.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.407G>T | p.Cys136Phe | missense_variant | Exon 5 of 9 | ENST00000371953.8 | NP_000305.3 | |
PTEN | NM_001304718.2 | c.-344G>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 4 of 9 | NP_001291647.1 | |||
PTEN | NM_001304717.5 | c.926G>T | p.Cys309Phe | missense_variant | Exon 6 of 10 | NP_001291646.4 | ||
PTEN | NM_001304718.2 | c.-344G>T | 5_prime_UTR_variant | Exon 4 of 9 | NP_001291647.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
The p.C136F pathogenic mutation (also known as c.407G>T), located in coding exon 5 of the PTEN gene, results from a G to T substitution at nucleotide position 407. The cysteine at codon 136 is replaced by phenylalanine, an amino acid with highly dissimilar properties. In a functional study, this variant demonstrated deficient phosphatase activity (Mighell TL et al. Am. J. Hum. Genet., 2018 05;102:943-955). Two other alterations at the same codon, p.C136R (c.406T>C) and p.C136Y (c.407G>A), have been detected in individuals with features consistent with PTEN Hamartoma Tumor Syndrome (PHTS) (Kubo Y et al. Br. J. Dermatol. 2000 Jun;142(6):1100-5; Galatola M et al. BMC Med. Genet., 2012 Apr;13:28; Matsumoto K et al. Diagn. Pathol. 2015 Sep;10:172; Ambry internal data). This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.