rs769719835
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000314.8(PTEN):c.174T>C(p.Asp58Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000278 in 1,438,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
PTEN
NM_000314.8 synonymous
NM_000314.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.54
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 10-87925522-T-C is Benign according to our data. Variant chr10-87925522-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 215730.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=5, Uncertain_significance=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PTEN | NM_000314.8 | c.174T>C | p.Asp58Asp | synonymous_variant | Exon 3 of 9 | ENST00000371953.8 | NP_000305.3 | |
| PTEN | NM_001304717.5 | c.693T>C | p.Asp231Asp | synonymous_variant | Exon 4 of 10 | NP_001291646.4 | ||
| PTEN | NM_001304718.2 | c.-541-5524T>C | intron_variant | Intron 2 of 8 | NP_001291647.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000418 AC: 1AN: 239268Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 129902
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GnomAD4 exome AF: 0.00000278 AC: 4AN: 1438654Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2AN XY: 716592
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:2
Nov 06, 2021
Sema4, Sema4
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: curation
- -
Mar 06, 2017
Color Diagnostics, LLC DBA Color Health
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Mar 09, 2018
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:2
Feb 25, 2019
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Aug 11, 2020
Quest Diagnostics Nichols Institute San Juan Capistrano
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
PTEN hamartoma tumor syndrome Benign:1
Nov 18, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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