chr10-87915833-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000314.8(PTEN):​c.165-9680G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 151,462 control chromosomes in the GnomAD database, including 761 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 0.093 ( 761 hom., cov: 32)

Consequence

PTEN
NM_000314.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.365

Publications

7 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: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTENNM_000314.8 linkc.165-9680G>C intron_variant Intron 2 of 8 ENST00000371953.8 NP_000305.3
PTENNM_001304717.5 linkc.684-9680G>C intron_variant Intron 3 of 9 NP_001291646.4 P60484
PTENNM_001304718.2 linkc.-541-15213G>C intron_variant Intron 2 of 8 NP_001291647.1 P60484

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTENENST00000371953.8 linkc.165-9680G>C intron_variant Intron 2 of 8 1 NM_000314.8 ENSP00000361021.3 P60484-1

Frequencies

GnomAD3 genomes
AF:
0.0927
AC:
14024
AN:
151344
Hom.:
759
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0568
Gnomad AMI
AF:
0.113
Gnomad AMR
AF:
0.162
Gnomad ASJ
AF:
0.143
Gnomad EAS
AF:
0.137
Gnomad SAS
AF:
0.0676
Gnomad FIN
AF:
0.0807
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.0956
Gnomad OTH
AF:
0.111
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0926
AC:
14028
AN:
151462
Hom.:
761
Cov.:
32
AF XY:
0.0919
AC XY:
6802
AN XY:
73992
show subpopulations
African (AFR)
AF:
0.0567
AC:
2339
AN:
41286
American (AMR)
AF:
0.162
AC:
2461
AN:
15204
Ashkenazi Jewish (ASJ)
AF:
0.143
AC:
495
AN:
3472
East Asian (EAS)
AF:
0.137
AC:
699
AN:
5114
South Asian (SAS)
AF:
0.0676
AC:
321
AN:
4746
European-Finnish (FIN)
AF:
0.0807
AC:
841
AN:
10422
Middle Eastern (MID)
AF:
0.153
AC:
45
AN:
294
European-Non Finnish (NFE)
AF:
0.0956
AC:
6491
AN:
67900
Other (OTH)
AF:
0.110
AC:
233
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
643
1285
1928
2570
3213
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
150
300
450
600
750
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0904
Hom.:
89
Bravo
AF:
0.0986
Asia WGS
AF:
0.107
AC:
372
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
4.4
DANN
Benign
0.53
PhyloP100
0.36
Mutation Taster
=100/0
polymorphism (auto)

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: rs1234223; hg19: chr10-89675590; API