13-19467353-TAAAAAAAA-TAAAAA

Position:

• chr13-19467353-TAAAAAAAA-TAAAAA

Variant summary

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

The NM_001395978.1(TPTE2):​c.393-12_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 0.0224 in 1,160,252 control chromosomes in the GnomAD database, including 109 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (100 hom., cov: 0)
  • Exomes 𝑓: 0.022 (9 hom.)
• Consequence: TPTE2 NM_001395978.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPTE2	NM_001395978.1	c.393-12_393-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000697147.1	NP_001382907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE2	ENST00000697147.1	c.393-12_393-10del		splice_polypyrimidine_tract_variant, intron_variant			NM_001395978.1	ENSP00000513136	P2

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3146 AN: 131638 Hom.: 100 Cov.: 0

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00934

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.000440

Gnomad SAS AF: 0.00696

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00730

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.0199

GnomAD3 exomes AF: 0.0401 AC: 1310 AN: 32670 Hom.: 1 AF XY: 0.0449 AC XY: 759 AN XY: 16922

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0676

Gnomad ASJ exome AF: 0.0797

Gnomad EAS exome AF: 0.0393

Gnomad SAS exome AF: 0.0757

Gnomad FIN exome AF: 0.00920

Gnomad NFE exome AF: 0.0329

Gnomad OTH exome AF: 0.0386

GnomAD4 exome AF: 0.0222 AC: 22861 AN: 1028608 Hom.: 9 AF XY: 0.0238 AC XY: 11951 AN XY: 502240

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0584

Gnomad4 ASJ exome AF: 0.0535

Gnomad4 EAS exome AF: 0.0298

Gnomad4 SAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.0295

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0305

GnomAD4 genome AF: 0.0239 AC: 3151 AN: 131644 Hom.: 100 Cov.: 0 AF XY: 0.0241 AC XY: 1516 AN XY: 62948

Gnomad4 AFR AF: 0.0765

Gnomad4 AMR AF: 0.00933

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.000442

Gnomad4 SAS AF: 0.00675

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00151

Gnomad4 OTH AF: 0.0198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;