GeneBe

rs34003473

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The NM_000314.8(PTEN):​c.802-11_802-3delTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000769 in 1,300,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 26)
Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

PTEN
NM_000314.8 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.37

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: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • 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: Likely_benign. The variant received -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 10-87960876-CTTTTTTTTT-C is Benign according to our data. Variant chr10-87960876-CTTTTTTTTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1529483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000314.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PTEN
NM_000314.8
MANE Select
c.802-11_802-3delTTTTTTTTT
splice_region intron
N/ANP_000305.3
PTEN
NM_001304717.5
c.1321-11_1321-3delTTTTTTTTT
splice_region intron
N/ANP_001291646.4
PTEN
NM_001304718.2
c.211-11_211-3delTTTTTTTTT
splice_region intron
N/ANP_001291647.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PTEN
ENST00000371953.8
TSL:1 MANE Select
c.802-17_802-9delTTTTTTTTT
intron
N/AENSP00000361021.3P60484-1
PTEN
ENST00000693560.1
c.1321-17_1321-9delTTTTTTTTT
intron
N/AENSP00000509861.1A0A8I5KSF9
PTEN
ENST00000700029.2
c.895-17_895-9delTTTTTTTTT
intron
N/AENSP00000514759.2A0A8V8TPK6

Frequencies

GnomAD3 genomes
Cov.:
26
GnomAD4 exome
AF:
7.69e-7
AC:
1
AN:
1300174
Hom.:
0
AF XY:
0.00000154
AC XY:
1
AN XY:
647380
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26382
American (AMR)
AF:
0.00
AC:
0
AN:
32672
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23504
East Asian (EAS)
AF:
0.0000280
AC:
1
AN:
35698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71378
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46632
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4954
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1005294
Other (OTH)
AF:
0.00
AC:
0
AN:
53660
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
26

ClinVar

ClinVar submissions
Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
1
Hereditary cancer-predisposing syndrome (1)
-
-
1
PTEN hamartoma tumor syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.4

Splicing

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

Publications

Other links and lift over

dbSNP: rs34003473; hg19: chr10-89720633; API