10-87895485-CA-CAA

Position:

• chr10-87895485-CA-CAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000314.8(PTEN):​c.164+1382dup variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10335 hom., cov: 0)
• Consequence: PTEN NM_000314.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTEN	NM_000314.8	c.164+1382dup		intron_variant		ENST00000371953.8
PTEN	NM_001304717.5	c.683+1382dup		intron_variant
PTEN	NM_001304718.2	c.-541+1382dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTEN	ENST00000371953.8	c.164+1382dup		intron_variant		1	NM_000314.8	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53399 AN: 151766 Hom.: 10331 Cov.: 0

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.352 AC: 53411 AN: 151884 Hom.: 10335 Cov.: 0 AF XY: 0.360 AC XY: 26734 AN XY: 74192

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.331

Alfa AF: 0.251 Hom.: 643

Bravo AF: 0.332

Asia WGS AF: 0.468 AC: 1619 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs3831732; hg19: chr10-89655242;