13-19467353-TAAAAAAAA-TAAAA

Position:

• chr13-19467353-TAAAAAAAA-TAAAA

Variant summary

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

The NM_001395978.1(TPTE2):​c.393-13_393-10del 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 0.00162 in 1,187,684 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: TPTE2 NM_001395978.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639

Genes affected

TPTE2 (HGNC:17299): (transmembrane phosphoinositide 3-phosphatase and tensin homolog 2) TPIP is a member of a large class of membrane-associated phosphatases with substrate specificity for the 3-position phosphate of inositol phospholipids.[supplied by OMIM, Jul 2002]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPTE2	NM_001395978.1	c.393-13_393-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000697147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPTE2	ENST00000697147.1	c.393-13_393-10del		splice_polypyrimidine_tract_variant, intron_variant			NM_001395978.1	P2

Frequencies

GnomAD3 genomes AF: 0.000251 AC: 33 AN: 131682 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000744

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000753

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000493

Gnomad OTH AF: 0.000552

GnomAD3 exomes AF: 0.00490 AC: 160 AN: 32670 Hom.: 0 AF XY: 0.00485 AC XY: 82 AN XY: 16922

Gnomad AFR exome AF: 0.0174

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.00946

Gnomad EAS exome AF: 0.00763

Gnomad SAS exome AF: 0.00971

Gnomad FIN exome AF: 0.000622

Gnomad NFE exome AF: 0.00402

Gnomad OTH exome AF: 0.00322

GnomAD4 exome AF: 0.00179 AC: 1893 AN: 1056000 Hom.: 0 AF XY: 0.00197 AC XY: 1014 AN XY: 515630

Gnomad4 AFR exome AF: 0.00852

Gnomad4 AMR exome AF: 0.00477

Gnomad4 ASJ exome AF: 0.00492

Gnomad4 EAS exome AF: 0.00221

Gnomad4 SAS exome AF: 0.00534

Gnomad4 FIN exome AF: 0.00232

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.00207

GnomAD4 genome AF: 0.000258 AC: 34 AN: 131684 Hom.: 0 Cov.: 0 AF XY: 0.000222 AC XY: 14 AN XY: 62968

Gnomad4 AFR AF: 0.000770

Gnomad4 AMR AF: 0.0000752

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000151

Gnomad4 NFE AF: 0.0000493

Gnomad4 OTH AF: 0.000549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs71092363; hg19: chr13-20041493;