Variant 13-19432475-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001395978.1(TPTE2):c.1220G>C(p.Arg407Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000922 in 1,573,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

TPTE2
NM_001395978.1 missense, splice_region

Scores

Splicing: ADA: 0.000009329

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03864947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPTE2	NM_001395978.1 linkuse as main transcript	c.1220G>C	p.Arg407Pro	missense_variant, splice_region_variant	19/23	ENST00000697147.1	NP_001382907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPTE2	ENST00000697147.1 linkuse as main transcript	c.1220G>C	p.Arg407Pro	missense_variant, splice_region_variant	19/23		NM_001395978.1	ENSP00000513136	P2	Q6XPS3-1

Frequencies

GnomAD3 genomes

AF:

0.0000706

AC:

AN:

127390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000850

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000233

Gnomad SAS

AF:

0.00116

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000168

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000183

AC:

AN:

246472

Hom.:

AF XY:

0.000225

AC XY:

AN XY:

133282

show subpopulations

Gnomad AFR exome

AF:

0.0000628

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.00133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000941

AC:

136

AN:

1445658

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

719220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.0000840

GnomAD4 genome

AF:

0.0000706

AC:

AN:

127496

Hom.:

Cov.:

AF XY:

0.0000821

AC XY:

AN XY:

60870

show subpopulations

Gnomad4 AFR

AF:

0.0000847

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000234

Gnomad4 SAS

AF:

0.00116

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000168

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.1220G>C (p.R407P) alteration is located in exon 17 (coding exon 16) of the TPTE2 gene. This alteration results from a G to C substitution at nucleotide position 1220, causing the arginine (R) at amino acid position 407 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.36

DEOGEN2

Uncertain

0.60

.;D;.;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.48

T;T;T;T;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.039

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.080

.;N;.;.;.

MutationTaster

Benign

0.98

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.9

D;D;D;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.27

T;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T

Polyphen

0.0

.;B;B;.;B

Vest4

0.50

MutPred

0.56

.;Gain of catalytic residue at S405 (P = 0);.;.;.;

MVP

0.41

MPC

0.38

ClinPred

0.036

GERP RS

1.4

Varity_R

0.26

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000093

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over