rs4915154

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002838.5(PTPRC):c.577A>G(p.Thr193Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,614,082 control chromosomes in the GnomAD database, including 1,595 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. T193T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.020 ( 177 hom., cov: 32)

Exomes 𝑓: 0.018 ( 1418 hom. )

Consequence

PTPRC
NM_002838.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.56

Publications

20 publications found

Variant links:

Genes affected

PTPRC (HGNC:9666): (protein tyrosine phosphatase receptor type C) 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, mitosis, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus is classified as a receptor type PTP. This PTP has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions through either direct interaction with components of the antigen receptor complexes, or by activating various Src family kinases required for the antigen receptor signaling. This PTP also suppresses JAK kinases, and thus functions as a regulator of cytokine receptor signaling. Alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jun 2012]

PTPRC Gene-Disease associations (from GenCC):

immunodeficiency 104
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
T-B+ severe combined immunodeficiency due to CD45 deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PTPRC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.523464E-4).

BP6

Variant 1-198702524-A-G is Benign according to our data. Variant chr1-198702524-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 464444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5 link	c.577A>G	p.Thr193Ala	missense_variant	Exon 6 of 33	ENST00000442510.8	NP_002829.3	P08575-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8 link	c.577A>G	p.Thr193Ala	missense_variant	Exon 6 of 33	1	NM_002838.5	ENSP00000411355.3		P08575-3

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3117

AN:

152078

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00536

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0600

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00784

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.0430

AC:

10805

AN:

251468

AF XY:

0.0388

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00854

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0185

AC:

26987

AN:

1461886

Hom.:

1418

Cov.:

AF XY:

0.0188

AC XY:

13696

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00364

AC:

122

AN:

33480

American (AMR)

AF:

0.118

AC:

5267

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00562

AC:

147

AN:

26136

East Asian (EAS)

AF:

0.196

AC:

7780

AN:

39700

South Asian (SAS)

AF:

0.0446

AC:

3846

AN:

86258

European-Finnish (FIN)

AF:

0.00165

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00730

AC:

8114

AN:

1112006

Other (OTH)

AF:

0.0259

AC:

1563

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1747

3494

5242

6989

8736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.0205

AC:

3120

AN:

152196

Hom.:

177

Cov.:

AF XY:

0.0223

AC XY:

1658

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00535

AC:

222

AN:

41518

American (AMR)

AF:

0.0602

AC:

921

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00750

AC:

AN:

3468

East Asian (EAS)

AF:

0.193

AC:

995

AN:

5164

South Asian (SAS)

AF:

0.0496

AC:

239

AN:

4822

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00782

AC:

532

AN:

67996

Other (OTH)

AF:

0.0260

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

139

279

418

558

697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0178

Hom.:

448

Bravo

AF:

0.0277

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.0393

AC:

4772

Asia WGS

AF:

0.134

AC:

464

AN:

3478

EpiCase

AF:

0.00802

EpiControl

AF:

0.00948

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 12716971, 16538473, 15333587) -

not specified

Benign:1

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency 105

Benign:1

Nov 08, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency 104

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0070

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.00085

T;T

MetaSVM

Benign

-1.1

PhyloP100

-4.6

PrimateAI

Benign

0.22

REVEL

Benign

0.069

Sift4G

Benign

0.27

T;T

Vest4

0.0070

MPC

0.17

ClinPred

0.0043

GERP RS

-12

Varity_R

0.043

gMVP

0.23

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over