13-19450160-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395978.1(TPTE2):ā€‹c.889A>Gā€‹(p.Met297Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000621 in 1,611,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

TPTE2
NM_001395978.1 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TPTE2NM_001395978.1 linkuse as main transcriptc.889A>G p.Met297Val missense_variant 16/23 ENST00000697147.1 NP_001382907.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TPTE2ENST00000697147.1 linkuse as main transcriptc.889A>G p.Met297Val missense_variant 16/23 NM_001395978.1 ENSP00000513136 P2Q6XPS3-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000364
AC:
9
AN:
247244
Hom.:
0
AF XY:
0.0000298
AC XY:
4
AN XY:
134088
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000492
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1458876
Hom.:
0
Cov.:
31
AF XY:
0.00000551
AC XY:
4
AN XY:
725766
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsFeb 07, 2023The c.889A>G (p.M297V) alteration is located in exon 14 (coding exon 13) of the TPTE2 gene. This alteration results from a A to G substitution at nucleotide position 889, causing the methionine (M) at amino acid position 297 to be replaced by a valine (V). 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
Uncertain
0.40
BayesDel_addAF
Benign
-0.029
T
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
.;D;.;.;.
Eigen
Benign
0.16
Eigen_PC
Benign
0.096
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.90
D;D;D;D;.
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.65
D;D;D;D;D
MetaSVM
Uncertain
-0.067
T
MutationAssessor
Benign
1.5
.;L;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D
REVEL
Pathogenic
0.71
Sift
Uncertain
0.0070
D;D;D;D;D
Sift4G
Benign
0.077
T;T;D;T;D
Polyphen
0.94, 0.86
.;P;P;.;P
Vest4
0.81
MutPred
0.45
.;Gain of catalytic residue at E296 (P = 0.0013);.;.;.;
MVP
0.62
MPC
0.86
ClinPred
0.40
T
GERP RS
2.8
Varity_R
0.60
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs764453510; hg19: chr13-20024300; API