Starting

Initialising…

PTEN

Final classification

VUS

PTEN c.-361C>T · p.?

PTEN

The PTEN NM_000314.8:c.-361C>T (NP_000305.3:p.?) variant has not been reported in ClinVar.

Gene

PTEN

Transcript

NM_000314.8

HGVS · transcript:coding

NM_000314.8:c.-361C>T

Consequence

N/A

GRCh38

chr10:87864109 C>T

GRCh37

chr10:89623866 C>T

Basis Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework was evaluated deterministically with applied criteria: BS1 supporting; no rule matched the adjudicated criteria. ▾

Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework was evaluated deterministically with applied criteria: BS1 supporting; no rule matched the adjudicated criteria.

Classification rationale

BS1 VUS

PTEN c.-361C>T

The PTEN NM_000314.8:c.-361C>T (NP_000305.3:p.?) variant has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 but present in gnomAD v4.1 at 6/492096 alleles, with filtering allele frequency 6.24e-06; this is above the PTEN PM2 cutoff and within the PTEN BS1_supporting frequency range.²

BS1 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗cspec ↗

Gene diagram · NM_000314.8 · variants mapped to exon structure

PTEN NM_000314.8

Fetching transcript structure from UCSC…

Applied criteria · 1 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

This variant is present in gnomAD v4.1 (AF= 1.21927e-05; MAF= 0.00122%, 6/492096 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 4.45315e-05; MAF= 0.00445%, 1/22456 alleles, homozygotes = 0); grpmax FAF= 6.24e-06.

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.0012% · 6 / 492,096
0 hom · FAF 0.00062%

Remaining individuals 1 / 22,456	0.0045%
European (non-Finnish) 5 / 279,178	0.0018%

+ 8 not observed (Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American)

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

COSMIC

Somatic evidence

COSMIC

This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant cancer hotspot.

COSMIC ↗

Sources & reference links

7Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC