10-87961150-T-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000314.8(PTEN):c.1026+32T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,578,496 control chromosomes in the GnomAD database, including 105,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.40 ( 12672 hom., cov: 31)
Exomes 𝑓: 0.36 ( 93105 hom. )
Consequence
PTEN
NM_000314.8 intron
NM_000314.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.850
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 10-87961150-T-G is Benign according to our data. Variant chr10-87961150-T-G is described in ClinVar as [Benign]. Clinvar id is 92810.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.1026+32T>G | intron_variant | ENST00000371953.8 | |||
PTEN | NM_001304717.5 | c.1545+32T>G | intron_variant | ||||
PTEN | NM_001304718.2 | c.436+32T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.1026+32T>G | intron_variant | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.399 AC: 60661AN: 151868Hom.: 12632 Cov.: 31
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GnomAD3 exomes AF: 0.373 AC: 92706AN: 248338Hom.: 17918 AF XY: 0.363 AC XY: 48929AN XY: 134850
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GnomAD4 exome AF: 0.358 AC: 511154AN: 1426510Hom.: 93105 Cov.: 28 AF XY: 0.355 AC XY: 252501AN XY: 711724
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GnomAD4 genome ? AF: 0.400 AC: 60753AN: 151986Hom.: 12672 Cov.: 31 AF XY: 0.398 AC XY: 29556AN XY: 74274
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 70% of patients studied by a panel of primary immunodeficiencies. Number of patients: 62. Only high quality variants are reported. - |
Cowden syndrome 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
PTEN hamartoma tumor syndrome Benign:2
Benign, reviewed by expert panel | curation | Clingen PTEN Variant Curation Expert Panel, Clingen | Sep 14, 2016 | PTEN c.1026+32T>G (IVS8+32T>G) meets criteria to be classified as benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BA1: Allele frequency of 0.374 (37.4%, 102,771/274,696 alleles) in the gnomAD cohort. (PMID 27535533) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 30316882) - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 06, 2020 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 26, 2020 | - - |
Macrocephaly-autism syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
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RBP_binding_hub_radar
RBP_regulation_power_radar
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