GeneBe

rs756623620

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_000314.8(PTEN):​c.493-13_493-12delTT variant causes a intron change. The variant allele was found at a frequency of 0.000000685 in 1,459,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTEN
NM_000314.8 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.85

Publications

0 publications found
Variant links:
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]
PTEN Gene-Disease associations (from GenCC):
  • Cowden syndrome 1
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
  • PTEN hamartoma tumor syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • macrocephaly-autism syndrome
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet
  • renal cell carcinoma
    Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
  • leiomyosarcoma
    Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
  • activated PI3K-delta syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Bannayan-Riley-Ruvalcaba syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Cowden disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Lhermitte-Duclos disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Proteus-like syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • glioma susceptibility 2
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 10-87952098-CTT-C is Benign according to our data. Variant chr10-87952098-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3904191.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTENNM_000314.8 linkc.493-13_493-12delTT intron_variant Intron 5 of 8 ENST00000371953.8 NP_000305.3
PTENNM_001304717.5 linkc.1012-13_1012-12delTT intron_variant Intron 6 of 9 NP_001291646.4 P60484
PTENNM_001304718.2 linkc.-99-13_-99-12delTT intron_variant Intron 5 of 8 NP_001291647.1 P60484

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTENENST00000371953.8 linkc.493-13_493-12delTT intron_variant Intron 5 of 8 1 NM_000314.8 ENSP00000361021.3 P60484-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459002
Hom.:
0
AF XY:
0.00000138
AC XY:
1
AN XY:
725918
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33408
American (AMR)
AF:
0.00
AC:
0
AN:
44650
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26118
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39644
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86126
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52424
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5466
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110862
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60304
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cowden syndrome 1 Benign:1
Feb 12, 2025
Myriad Genetics, Inc.
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs756623620; hg19: chr10-89711855; API