1-198699632-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002838.5(PTPRC):c.367G>C(p.Asp123His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 1,614,164 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 23 hom., cov: 32)

Exomes 𝑓: 0.016 ( 265 hom. )

Consequence

PTPRC
NM_002838.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.27

Publications

15 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=0.0033371449).

BP6

Variant 1-198699632-G-C is Benign according to our data. Variant chr1-198699632-G-C is described in ClinVar as Benign. ClinVar VariationId is 138847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0139 (2123/152278) while in subpopulation NFE AF = 0.0161 (1094/68010). AF 95% confidence interval is 0.0153. There are 23 homozygotes in GnomAd4. There are 1129 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRC	NM_002838.5 link	c.367G>C	p.Asp123His	missense_variant	Exon 5 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.367G>C	p.Asp123His	missense_variant	Exon 5 of 33	1	NM_002838.5	ENSP00000411355.3		P08575-3

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2111

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00519

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0489

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.0148

AC:

3714

AN:

251398

AF XY:

0.0152

show subpopulations

Gnomad AFR exome

AF:

0.00603

Gnomad AMR exome

AF:

0.00775

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.0487

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.0160

AC:

23408

AN:

1461886

Hom.:

265

Cov.:

AF XY:

0.0160

AC XY:

11602

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00499

AC:

167

AN:

33480

American (AMR)

AF:

0.00783

AC:

350

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00417

AC:

109

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0123

AC:

1065

AN:

86258

European-Finnish (FIN)

AF:

0.0474

AC:

2533

AN:

53420

Middle Eastern (MID)

AF:

0.0147

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0164

AC:

18238

AN:

1112006

Other (OTH)

AF:

0.0142

AC:

859

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1447

2894

4340

5787

7234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.0139

AC:

2123

AN:

152278

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1129

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00544

AC:

226

AN:

41570

American (AMR)

AF:

0.0108

AC:

165

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.0124

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0489

AC:

519

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0161

AC:

1094

AN:

68010

Other (OTH)

AF:

0.0147

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

100

200

301

401

501

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:

0.0142

Hom.:

Bravo

AF:

0.0103

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.0178

AC:

153

ExAC

AF:

0.0139

AC:

1684

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0167

EpiControl

AF:

0.0150

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

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;.;T;.;T

Eigen

Benign

0.079

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.79

T;T;T;T;T

MetaRNN

Benign

0.0033

T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

1.3

PrimateAI

Benign

0.33

REVEL

Benign

0.070

Sift4G

Benign

0.11

.;T;T;.;D

Vest4

0.13

MPC

0.70

ClinPred

0.0088

GERP RS

3.3

Varity_R

0.10

gMVP

0.21

Mutation Taster

=98/2

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