chr10-87960930-A-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_000314.8(PTEN):āc.838A>Cā(p.Ile280Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I280V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000314.8 missense
Scores
Clinical Significance
Conservation
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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.838A>C | p.Ile280Leu | missense_variant | 8/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.1357A>C | p.Ile453Leu | missense_variant | 9/10 | ||
PTEN | NM_001304718.2 | c.247A>C | p.Ile83Leu | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.838A>C | p.Ile280Leu | missense_variant | 8/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460876Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 726706
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2023 | The p.I280L variant (also known as c.838A>C), located in coding exon 8 of the PTEN gene, results from an A to C substitution at nucleotide position 838. The isoleucine at codon 280 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at