13-19467353-TAAAAAAAA-TAAAAAA

Position:

• chr13-19467353-TAAAAAAAA-TAAAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001395978.1(TPTE2):​c.393-11_393-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (965 hom., cov: 0)
  • Exomes 𝑓: 0.22 (60 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPTE2 NM_001395978.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 13-19467353-TAA-T is Benign according to our data. Variant chr13-19467353-TAA-T is described in ClinVar as [Benign]. Clinvar id is 403563.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPTE2	NM_001395978.1	c.393-11_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.393-11_393-10del		splice_polypyrimidine_tract_variant, intron_variant			NM_001395978.1	ENSP00000513136	P2

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 12201 AN: 131622 Hom.: 964 Cov.: 0

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0501

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0746

GnomAD3 exomes AF: 0.188 AC: 6154 AN: 32670 Hom.: 5 AF XY: 0.196 AC XY: 3314 AN XY: 16922

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.241

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.204

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.220

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.224 AC: 215759 AN: 961740 Hom.: 60 AF XY: 0.227 AC XY: 106697 AN XY: 470242

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.0929 AC: 12223 AN: 131622 Hom.: 965 Cov.: 0 AF XY: 0.0921 AC XY: 5799 AN XY: 62930

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.0579

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0384

Gnomad4 OTH AF: 0.0742

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;