20-42085817-A-T

Position:

chr20-42085817-A-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_007050.6(PTPRT):c.3883T>A(p.Cys1295Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,613,620 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

PTPRT
NM_007050.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.03

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.

PP2

Missense variant where missense usually causes diseases, PTPRT

BP4

Computational evidence support a benign effect (MetaRNN=0.0122152865).

BP6

Variant 20-42085817-A-T is Benign according to our data. Variant chr20-42085817-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048700.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRT	NM_007050.6 linkuse as main transcript	c.3883T>A	p.Cys1295Ser	missense_variant	28/31	ENST00000373187.6
LOC101927182	XR_001754611.2 linkuse as main transcript	n.378-4762A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRT	ENST00000373187.6 linkuse as main transcript	c.3883T>A	p.Cys1295Ser	missense_variant	28/31	1	NM_007050.6	P4	O14522-3

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

240

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00560

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.000959

GnomAD3 exomes

AF:

0.000401

AC:

100

AN:

249448

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00575

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.000151

AC:

220

AN:

1461370

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.00547

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152250

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00556

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.00173

ESP6500AA

AF:

0.00436

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000496

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PTPRT-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 11, 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

0.22

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

T;T;T;T;.;T;.;.

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

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

M_CAP

Benign

0.073

MetaRNN

Benign

0.012

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

MetaSVM

Benign

-0.29

MutationAssessor

Benign

0.25

N;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

N;N;N;N;.;N;.;.

REVEL

Uncertain

0.47

Sift

Benign

0.12

T;T;T;T;.;T;.;.

Sift4G

Benign

0.41

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

Polyphen

0.54

P;.;.;.;.;.;.;P

Vest4

0.35

MutPred

0.45

Gain of disorder (P = 3e-04);.;.;.;.;.;.;.;

MVP

0.40

MPC

1.3

ClinPred

0.084

GERP RS

5.3

Varity_R

0.23

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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