20-42082003-C-T

Position:

chr20-42082003-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_007050.6(PTPRT):c.4151G>A(p.Arg1384His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,614,206 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 39 hom. )

Consequence

PTPRT
NM_007050.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.88

Variant links:

Genes affected

PTPRT (HGNC:9682): (protein tyrosine phosphatase receptor type T) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracellular catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP (MAM) domain, Ig-like and fibronectin type III-like repeats. The protein domain structure and the expression pattern of the mouse counterpart of this PTP suggest its roles in both signal transduction and cellular adhesion in the central nervous system. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRT links:

LOC101927182 (HGNC:):

LOC101927182 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, phyloP100way_vertebrate, PrimateAI, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0153517425).

BP6

Variant 20-42082003-C-T is Benign according to our data. Variant chr20-42082003-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652338.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 663 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRT	NM_007050.6 linkuse as main transcript	c.4151G>A	p.Arg1384His	missense_variant	30/31	ENST00000373187.6	NP_008981.4
LOC101927182	XR_001754611.2 linkuse as main transcript	n.378-8576C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRT	ENST00000373187.6 linkuse as main transcript	c.4151G>A	p.Arg1384His	missense_variant	30/31	1	NM_007050.6	ENSP00000362283	P4	O14522-3

Frequencies

GnomAD3 genomes

AF:

0.00436

AC:

663

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00510

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00596

AC:

1486

AN:

249466

Hom.:

AF XY:

0.00586

AC XY:

793

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.000969

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.0237

Gnomad NFE exome

AF:

0.00789

Gnomad OTH exome

AF:

0.00610

GnomAD4 exome

AF:

0.00475

AC:

6943

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

3376

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.0257

Gnomad4 NFE exome

AF:

0.00469

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00435

AC:

663

AN:

152334

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0245

Gnomad4 NFE

AF:

0.00510

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00430

Hom.:

Bravo

AF:

0.00255

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00144

AC:

ESP6500EA

AF:

0.00498

AC:

ExAC

AF:

0.00716

AC:

866

EpiCase

AF:

0.00496

EpiControl

AF:

0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

PTPRT: PP2, BS2 -

PTPRT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 22, 2019

This variant is classified as 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

Pathogenic

0.71

BayesDel_addAF

Benign

0.0045

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.84

D;D;D;D;.;D;.;.

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.97

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;D

MetaRNN

Benign

0.015

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.0042

MutationAssessor

Pathogenic

4.1

H;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.8

D;D;D;D;.;D;.;.

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

D;D;D;D;.;D;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;.;.;.;D

Vest4

0.89

MVP

0.90

MPC

1.8

ClinPred

0.11

GERP RS

6.1

Varity_R

0.52

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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