dbSNP rs368482243: TPTE2:p.Cys433Tyr (chr13-19430472-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001395978.1(TPTE2):c.1298G>A(p.Cys433Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,607,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

TPTE2
NM_001395978.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.945

Publications

2 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.40228933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395978.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPTE2	NM_001395978.1	MANE Select	c.1298G>A	p.Cys433Tyr	missense	Exon 20 of 23	NP_001382907.1	Q6XPS3-1
TPTE2	NM_199254.3		c.1298G>A	p.Cys433Tyr	missense	Exon 18 of 21	NP_954863.2	Q6XPS3-1
TPTE2	NM_130785.4		c.1067G>A	p.Cys356Tyr	missense	Exon 15 of 18	NP_570141.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPTE2	ENST00000697147.1	MANE Select	c.1298G>A	p.Cys433Tyr	missense	Exon 20 of 23	ENSP00000513136.1	Q6XPS3-1
TPTE2	ENST00000390680.2	TSL:1	c.1067G>A	p.Cys356Tyr	missense	Exon 15 of 18	ENSP00000375098.2	Q6XPS3-3
TPTE2	ENST00000696858.2		c.1298G>A	p.Cys433Tyr	missense	Exon 19 of 22	ENSP00000512931.1	Q6XPS3-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000245

AC:

AN:

244634

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.000374

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000962

AC:

AN:

1455522

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724076

show subpopulations

African (AFR)

AF:

0.000392

AC:

AN:

33142

American (AMR)

AF:

0.00

AC:

AN:

42848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25998

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.00

AC:

AN:

84814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109920

Other (OTH)

AF:

0.0000166

AC:

AN:

60152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.000386

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.77

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.65

M_CAP

Benign

0.0043

MetaRNN

Benign

0.40

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.2

PhyloP100

0.94

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-8.7

REVEL

Benign

0.26

Sift

Benign

0.068

Sift4G

Uncertain

0.012

Polyphen

0.99

Vest4

0.36

MVP

0.80

MPC

1.1

ClinPred

0.27

GERP RS

1.4

Varity_R

0.57

gMVP

0.75

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over