18-7774192-T-A

Position:

chr18-7774192-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001105244.2(PTPRM):c.117T>A(p.Ser39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,612,842 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.020 ( 93 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 99 hom. )

Consequence

PTPRM
NM_001105244.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

PTPRM (HGNC:9675): (protein tyrosine phosphatase receptor type M) 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 catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP has been shown to mediate cell-cell aggregation through the interaction with another molecule of this PTP on an adjacent cell. This PTP can interact with scaffolding protein RACK1/GNB2L1, which may be necessary for the downstream signaling in response to cell-cell adhesion. Alternative splicing results in multiple transcripts encoding distinct isoforms. [provided by RefSeq, Jul 2008]

PTPRM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00657779).

BP6

Variant 18-7774192-T-A is Benign according to our data. Variant chr18-7774192-T-A is described in ClinVar as [Benign]. Clinvar id is 773336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRM	NM_001105244.2 linkuse as main transcript	c.117T>A	p.Ser39Arg	missense_variant	2/33	ENST00000580170.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRM	ENST00000580170.6 linkuse as main transcript	c.117T>A	p.Ser39Arg	missense_variant	2/33	1	NM_001105244.2	A1	P28827-2
PTPRM	ENST00000332175.12 linkuse as main transcript	c.117T>A	p.Ser39Arg	missense_variant	2/31	1		P4	P28827-1
PTPRM	ENST00000400053.8 linkuse as main transcript	c.-70T>A		5_prime_UTR_variant	2/31	5
PTPRM	ENST00000400060.8 linkuse as main transcript	c.-3442T>A		5_prime_UTR_variant	1/32	5

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2992

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000558

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00564

AC:

1419

AN:

251418

Hom.:

AF XY:

0.00441

AC XY:

599

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0725

Gnomad AMR exome

AF:

0.00390

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00236

AC:

3443

AN:

1460526

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

1508

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.0751

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.000280

Gnomad4 OTH exome

AF:

0.00495

GnomAD4 genome

AF:

0.0197

AC:

3000

AN:

152316

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1417

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0672

Gnomad4 AMR

AF:

0.00849

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.0230

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0635

AC:

280

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00628

AC:

763

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000873

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

PTPRM-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 17, 2020

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

Uncertain

0.35

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.18

Sift

Benign

0.18

.;T

Sift4G

Benign

0.17

T;T

Polyphen

1.0

.;D

Vest4

0.64

MutPred

0.28

Gain of catalytic residue at S39 (P = 0.0576);Gain of catalytic residue at S39 (P = 0.0576);

MVP

0.75

MPC

1.1

ClinPred

0.028

GERP RS

1.6

Varity_R

0.64

gMVP

0.82

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