chr10-87933180-C-G
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP2PP3_Moderate
The NM_000314.8(PTEN):c.421C>G(p.His141Asp) 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H141P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000314.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.421C>G | p.His141Asp | missense_variant | 5/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.940C>G | p.His314Asp | missense_variant | 6/10 | ||
PTEN | NM_001304718.2 | c.-330C>G | 5_prime_UTR_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.421C>G | p.His141Asp | 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
PTEN hamartoma tumor syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2016 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PTEN-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This sequence change replaces histidine with aspartic acid at codon 141 of the PTEN protein (p.His141Asp). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at