Genetic Information

Gene & Transcript Details

Gene
PTEN
Transcript
NM_000314.8 MANE Select
Total Exons
—
Reference Sequence
NC_000010.10
Alternative Transcripts
IDStatusDetails
NM_000314.7 RefSeq Select 8514 nt | 845–2056
NM_000314.5 Alternative 8719 nt | 1032–2243
NM_000314.4 Alternative 5572 nt | 1032–2243
NM_000314.3 Alternative 3416 nt | 1032–2243
NM_000314.6 Alternative 8718 nt | 1032–2243
NM_000314.8 MANE Select 8515 nt | 846–2057

Variant Details

HGVS Notation
NM_000314.8:c.525del
Protein Change
Y176Ifs*7
Location
Exon 6 (Exon 6 of )
6
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Pathogenic
1 publications
Publications List
PMID: 9467011

For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). This sequence change deletes 1 nucleotide from exon 6 of the PTEN mRNA (c.525delG), causing a frameshift at codon 176. This creates a premature translational stop signal (p.Tyr176Ilefs*7) and is expected to result in an absent or disrupted protein product.

Clinical Statement

"This variant has been reported in ClinVar as Pathogenic (1 clinical laboratories)."

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene PTEN.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: PTENY176Ifs*7PTENY176Ifs*7SomaticNCBI Gene:5728|Show additional gene information Variant OverviewPTEN, a lipid and protein phosphatase, is one of the most frequently mutated genes in cancer.The PTEN Y176Ifs*7 is a truncating mutation in a tumor suppressor gene, and therefore is likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in PTEN is: PTEN truncating mutations can produce several forms of C-terminally truncated PTEN proteins. Truncating mutations closer to the N-terminus result in loss of PTEN phosphatase function and an inability to negatively regulate PI3K/AKT pathway activity (PMID: 11237521). Expression of a PTEN truncation mutation in mouse embryonic fibroblasts demonstrated that these mutations are oncogenic and increase genome fragility due to the inability of PTEN to associate with chromosomal centromeres compared to the full-length protein (PMID: 17218262). JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Unknown
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.02 -31 bp
- Donor Loss (DL) 0.01 110 bp
+ Acceptor Gain (AG) 0.0 13 bp
+ Donor Gain (DG) 0.0 -31 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PVS1

PVS1 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PP5

PP5 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)