13-19467353-TAAAAAAAA-TAAAAAA

Variant names:

• chr13-19467353-TAA-T
• rs71092363
• NM_001395978.1:c.393-11_393-10delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001395978.1(TPTE2):​c.393-11_393-10delTT variant causes a 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 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TPTE2	NM_001395978.1	c.393-11_393-10delTT		intron_variant	Intron 9 of 22	ENST00000697147.1	NP_001382907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPTE2	ENST00000697147.1	c.393-11_393-10delTT		intron_variant	Intron 9 of 22		NM_001395978.1	ENSP00000513136.1

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

GnomAD2 exomes AF: 0.188 AC: 6154 AN: 32670 AF XY: 0.196

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.256 AC: 5587 AN: 21848

American (AMR) AF: 0.265 AC: 2789 AN: 10510

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 3643 AN: 15098

East Asian (EAS) AF: 0.292 AC: 6917 AN: 23690

South Asian (SAS) AF: 0.252 AC: 9597 AN: 38114

European-Finnish (FIN) AF: 0.212 AC: 7233 AN: 34126

Middle Eastern (MID) AF: 0.243 AC: 849 AN: 3492

European-Non Finnish (NFE) AF: 0.219 AC: 169773 AN: 775066

Other (OTH) AF: 0.235 AC: 9371 AN: 39796

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.225 AC: 8178 AN: 36326

American (AMR) AF: 0.0579 AC: 770 AN: 13288

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 165 AN: 3196

East Asian (EAS) AF: 0.0199 AC: 90 AN: 4530

South Asian (SAS) AF: 0.0700 AC: 280 AN: 4000

European-Finnish (FIN) AF: 0.0314 AC: 207 AN: 6598

Middle Eastern (MID) AF: 0.101 AC: 25 AN: 248

European-Non Finnish (NFE) AF: 0.0384 AC: 2332 AN: 60798

Other (OTH) AF: 0.0742 AC: 135 AN: 1820

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs71092363; hg19: chr13-20041493;