rs11355437

chr10-87879299-AG-A

Variant summary

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

The NM_000314.8(PTEN):c.80-14725del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,772 control chromosomes in the GnomAD database, including 10,254 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10254 hom., cov: 0)
• Consequence: PTEN NM_000314.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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 = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTEN	NM_000314.8	c.80-14725del		intron_variant		ENST00000371953.8
PTEN	NM_001304717.5	c.599-14725del		intron_variant
PTEN	NM_001304718.2	c.-625-14725del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTEN	ENST00000371953.8	c.80-14725del		intron_variant		1	NM_000314.8	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53018 AN: 151654 Hom.: 10250 Cov.: 0

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.349 AC: 53028 AN: 151772 Hom.: 10254 Cov.: 0 AF XY: 0.358 AC XY: 26586 AN XY: 74180

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.332

Alfa AF: 0.249 Hom.: 641

Bravo AF: 0.327

Asia WGS AF: 0.476 AC: 1653 AN: 3478

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: rs11355437; hg19: chr10-89639056;