rs34003473

chr10-87960876-CTTTTTTTTT-Cchr10-87960876-CTTTTTTTTT-CTchr10-87960876-CTTTTTTTTT-CTTTTchr10-87960876-CTTTTTTTTT-CTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTchr10-87960876-CTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000314.8(PTEN):c.802-11_802-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000769 in 1,300,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: PTEN NM_000314.8 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-87960876-CTTTTTTTTT-C is Benign according to our data. Variant chr10-87960876-CTTTTTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1529483.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTEN	NM_000314.8	c.802-11_802-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371953.8
PTEN	NM_001304717.5	c.1321-11_1321-3del		intron_variant
PTEN	NM_001304718.2	c.212-11_212-3del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTEN	ENST00000371953.8	c.802-11_802-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000314.8	P1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 7.69e-7 AC: 1 AN: 1300174 Hom.: 0 AF XY: 0.00000154 AC XY: 1 AN XY: 647380

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PTEN hamartoma tumor syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-89720633;