chr10-87913812-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000314.8(PTEN):c.165-11701C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,600 control chromosomes in the GnomAD database, including 12,449 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.40 ( 12449 hom., cov: 31)
Consequence
PTEN
NM_000314.8 intron
NM_000314.8 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.627
Publications
8 publications found
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 1Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
- PTEN hamartoma tumor syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- macrocephaly-autism syndromeInheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet
- renal cell carcinomaInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- leiomyosarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- activated PI3K-delta syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Bannayan-Riley-Ruvalcaba syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Cowden diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Lhermitte-Duclos diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Proteus-like syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- glioma susceptibility 2Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.165-11701C>T | intron_variant | Intron 2 of 8 | ENST00000371953.8 | NP_000305.3 | ||
PTEN | NM_001304717.5 | c.684-11701C>T | intron_variant | Intron 3 of 9 | NP_001291646.4 | |||
PTEN | NM_001304718.2 | c.-541-17234C>T | intron_variant | Intron 2 of 8 | NP_001291647.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.397 AC: 60068AN: 151482Hom.: 12410 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
60068
AN:
151482
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.397 AC: 60158AN: 151600Hom.: 12449 Cov.: 31 AF XY: 0.395 AC XY: 29284AN XY: 74102 show subpopulations
GnomAD4 genome
AF:
AC:
60158
AN:
151600
Hom.:
Cov.:
31
AF XY:
AC XY:
29284
AN XY:
74102
show subpopulations
African (AFR)
AF:
AC:
20451
AN:
41304
American (AMR)
AF:
AC:
6870
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
AC:
1299
AN:
3458
East Asian (EAS)
AF:
AC:
2598
AN:
5162
South Asian (SAS)
AF:
AC:
1412
AN:
4806
European-Finnish (FIN)
AF:
AC:
3580
AN:
10396
Middle Eastern (MID)
AF:
AC:
127
AN:
294
European-Non Finnish (NFE)
AF:
AC:
22706
AN:
67910
Other (OTH)
AF:
AC:
868
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1773
3546
5318
7091
8864
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
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550
1100
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2750
<30
30-35
35-40
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1558
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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