NM_002838.5:c.1029G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002838.5(PTPRC):c.1029G>A(p.Gln343Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 1,605,048 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 25 hom., cov: 33)

Exomes 𝑓: 0.016 ( 268 hom. )

Consequence

PTPRC
NM_002838.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.447

Publications

3 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-198708257-G-A is Benign according to our data. Variant chr1-198708257-G-A is described in ClinVar as Benign. ClinVar VariationId is 138849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.447 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0141 (2142/152258) while in subpopulation NFE AF = 0.0159 (1084/68012). AF 95% confidence interval is 0.0152. There are 25 homozygotes in GnomAd4. There are 1133 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5 link	c.1029G>A	p.Gln343Gln	synonymous_variant	Exon 10 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.1029G>A	p.Gln343Gln	synonymous_variant	Exon 10 of 33	1	NM_002838.5	ENSP00000411355.3		P08575-3

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2136

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00512

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0493

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0159

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0150

AC:

3757

AN:

250326

AF XY:

0.0155

show subpopulations

Gnomad AFR exome

AF:

0.00503

Gnomad AMR exome

AF:

0.00754

Gnomad ASJ exome

AF:

0.0193

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0486

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.0160

AC:

23173

AN:

1452790

Hom.:

268

Cov.:

AF XY:

0.0159

AC XY:

11467

AN XY:

722920

show subpopulations

African (AFR)

AF:

0.00505

AC:

168

AN:

33262

American (AMR)

AF:

0.00761

AC:

339

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.0180

AC:

465

AN:

25882

East Asian (EAS)

AF:

0.0000507

AC:

AN:

39418

South Asian (SAS)

AF:

0.0117

AC:

1007

AN:

86052

European-Finnish (FIN)

AF:

0.0474

AC:

2508

AN:

52894

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

5320

European-Non Finnish (NFE)

AF:

0.0160

AC:

17719

AN:

1105520

Other (OTH)

AF:

0.0150

AC:

897

AN:

59894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

1009

2018

3027

4036

5045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.0141

AC:

2142

AN:

152258

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1133

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00522

AC:

217

AN:

41566

American (AMR)

AF:

0.0106

AC:

162

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0112

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0493

AC:

521

AN:

10570

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0159

AC:

1084

AN:

68012

Other (OTH)

AF:

0.0114

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0153

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.00579

AC:

AN:

3470

EpiCase

AF:

0.0169

EpiControl

AF:

0.0149

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 02, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Immunodeficiency 104

Benign:1

Feb 01, 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

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.15

(source)

DANN

Benign

0.31

PhyloP100

-0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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