Genetic Variant TPTE2:c.393-12_393-10delTTT (chr13-19467353-TAAA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001395978.1(TPTE2):c.393-12_393-10delTTT variant causes a 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 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

0 publications found

Variant links:

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]

TPTE2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TPTE2	NM_001395978.1 link	c.393-12_393-10delTTT		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 link	c.393-12_393-10delTTT		intron_variant	Intron 9 of 22		NM_001395978.1	ENSP00000513136.1		Q6XPS3-1

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3146

AN:

131638

Hom.:

100

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0401

AC:

1310

AN:

32670

AF XY:

0.0449

show subpopulations

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 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.:

AF XY:

0.0238

AC XY:

11951

AN XY:

502240

show subpopulations

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

African (AFR)

AF:

0.102

AC:

2252

AN:

22146

American (AMR)

AF:

0.0584

AC:

620

AN:

10610

Ashkenazi Jewish (ASJ)

AF:

0.0535

AC:

832

AN:

15544

East Asian (EAS)

AF:

0.0298

AC:

731

AN:

24514

South Asian (SAS)

AF:

0.0500

AC:

1952

AN:

39056

European-Finnish (FIN)

AF:

0.0295

AC:

1021

AN:

34646

Middle Eastern (MID)

AF:

0.0301

AC:

108

AN:

3584

European-Non Finnish (NFE)

AF:

0.0168

AC:

14064

AN:

836514

Other (OTH)

AF:

0.0305

AC:

1281

AN:

41994

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.296

Heterozygous variant carriers

1851

3702

5553

7404

9255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0239

AC:

3151

AN:

131644

Hom.:

100

Cov.:

AF XY:

0.0241

AC XY:

1516

AN XY:

62948

show subpopulations

African (AFR)

AF:

0.0765

AC:

2781

AN:

36340

American (AMR)

AF:

0.00933

AC:

124

AN:

13288

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3192

East Asian (EAS)

AF:

0.000442

AC:

AN:

4530

South Asian (SAS)

AF:

0.00675

AC:

AN:

3998

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

6598

Middle Eastern (MID)

AF:

0.00806

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.00151

AC:

AN:

60812

Other (OTH)

AF:

0.0198

AC:

AN:

1820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

140

280

419

559

699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

13-19467353-TAAAAAAAA-TAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over