GeneBe

rs1554826068

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000314.8(PTEN):​c.*3T>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000000686 in 1,458,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

PTEN
NM_000314.8 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

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;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTENNM_000314.8 linkc.*3T>A 3_prime_UTR_variant Exon 9 of 9 ENST00000371953.8 NP_000305.3
PTENNM_001304717.5 linkc.*3T>A 3_prime_UTR_variant Exon 10 of 10 NP_001291646.4 P60484
PTENNM_001304718.2 linkc.*3T>A 3_prime_UTR_variant Exon 9 of 9 NP_001291647.1 P60484

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTENENST00000371953.8 linkc.*3T>A 3_prime_UTR_variant Exon 9 of 9 1 NM_000314.8 ENSP00000361021.3 P60484-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458680
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
725548
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33262
American (AMR)
AF:
0.00
AC:
0
AN:
44262
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26008
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39642
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85490
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53274
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5748
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1110784
Other (OTH)
AF:
0.00
AC:
0
AN:
60210
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

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.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1
Nov 23, 2018
Color Diagnostics, LLC DBA Color Health
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
15
DANN
Benign
0.89
PhyloP100
4.4

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: rs1554826068; hg19: chr10-89725232; API