chr12-15322757-G-T

Position:

chr12-15322757-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000281171.9(PTPRO):c.31G>T(p.Ala11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,611,168 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 6 hom. )

Consequence

PTPRO
ENST00000281171.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

PTPRO (HGNC:9678): (protein tyrosine phosphatase receptor type O) This gene encodes a member of the R3 subtype family of receptor-type protein tyrosine phosphatases. These proteins are localized to the apical surface of polarized cells and may have tissue-specific functions through activation of Src family kinases. This gene contains two distinct promoters, and alternatively spliced transcript variants encoding multiple isoforms have been observed. The encoded proteins may have multiple isoform-specific and tissue-specific functions, including the regulation of osteoclast production and activity, inhibition of cell proliferation and facilitation of apoptosis. This gene is a candidate tumor suppressor, and decreased expression of this gene has been observed in several types of cancer. [provided by RefSeq, May 2011]

PTPRO links:

LOC105369673 (HGNC:):

LOC105369673 links:

RERG (HGNC:15980): (RAS like estrogen regulated growth inhibitor) RERG, a member of the RAS superfamily of GTPases, inhibits cell proliferation and tumor formation (Finlin et al., 2001 [PubMed 11533059]).[supplied by OMIM, Mar 2009]

RERG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035243034).

BP6

Variant 12-15322757-G-T is Benign according to our data. Variant chr12-15322757-G-T is described in ClinVar as [Benign]. Clinvar id is 1614800.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRO	NM_030667.3 linkuse as main transcript	c.31G>T	p.Ala11Ser	missense_variant	1/27	ENST00000281171.9	NP_109592.1
LOC105369673	XR_007063224.1 linkuse as main transcript	n.332+14620C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRO	ENST00000281171.9 linkuse as main transcript	c.31G>T	p.Ala11Ser	missense_variant	1/27	1	NM_030667.3	ENSP00000281171	P4	Q16827-1

Frequencies

GnomAD3 genomes

AF:

0.000834

AC:

127

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000814

AC:

196

AN:

240906

Hom.:

AF XY:

0.000926

AC XY:

122

AN XY:

131704

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000321

Gnomad ASJ exome

AF:

0.00617

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.000197

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00107

AC:

1567

AN:

1458870

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

765

AN XY:

725696

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00756

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000814

Gnomad4 FIN exome

AF:

0.000114

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152298

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00142

Hom.:

Bravo

AF:

0.000805

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000719

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.00154

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 14, 2023

- -

PTPRO-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 30, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.9

DANN

Benign

0.84

DEOGEN2

Benign

0.092

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.0035

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.34

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.30

N;N;N

REVEL

Benign

0.027

Sift

Uncertain

0.011

D;T;D

Sift4G

Benign

0.076

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.044

MVP

0.14

MPC

0.25

ClinPred

0.0032

GERP RS

-2.1

Varity_R

0.11

gMVP

0.29

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

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