rs1044487
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000314.8(PTEN):c.*65T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000696 in 143,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000070 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000024 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PTEN
NM_000314.8 3_prime_UTR
NM_000314.8 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.80
Genes affected
PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
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Computational evidence support a benign effect (BayesDel_noAF=-0.4).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.*65T>C | 3_prime_UTR_variant | 9/9 | ENST00000371953.8 | ||
PTEN | NM_001304717.5 | c.*65T>C | 3_prime_UTR_variant | 10/10 | |||
PTEN | NM_001304718.2 | c.*65T>C | 3_prime_UTR_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.*65T>C | 3_prime_UTR_variant | 9/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000696 AC: 1AN: 143604Hom.: 0 Cov.: 31
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000241 AC: 1AN: 414308Hom.: 0 Cov.: 9 AF XY: 0.00000491 AC XY: 1AN XY: 203670
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GnomAD4 genome ? AF: 0.00000696 AC: 1AN: 143604Hom.: 0 Cov.: 31 AF XY: 0.0000143 AC XY: 1AN XY: 69694
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ClinVar
Not reported inComputational scores
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Benign
CADD
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at