1-198735165-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002838.5(PTPRC):c.2316C>T(p.Gly772Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,602,070 control chromosomes in the GnomAD database, including 18,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2562 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16147 hom. )

Consequence

PTPRC
NM_002838.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.704

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-198735165-C-T is Benign according to our data. Variant chr1-198735165-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.704 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002838.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRC	NM_002838.5	MANE Select	c.2316C>T	p.Gly772Gly	synonymous	Exon 23 of 33	NP_002829.3
	PTPRC	NM_080921.4		c.1833C>T	p.Gly611Gly	synonymous	Exon 20 of 30	NP_563578.2	P08575-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRC	ENST00000442510.8	TSL:1 MANE Select	c.2316C>T	p.Gly772Gly	synonymous	Exon 23 of 33	ENSP00000411355.3	P08575-3
PTPRC	ENST00000348564.12	TSL:1	c.1833C>T	p.Gly611Gly	synonymous	Exon 20 of 30	ENSP00000306782.7	P08575-4
PTPRC	ENST00000529828.5	TSL:1	n.2172C>T		non_coding_transcript_exon	Exon 22 of 22	ENSP00000469141.1	A0A075B788

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25869

AN:

151374

Hom.:

2554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.0835

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.0674

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.164

GnomAD2 exomes

AF:

0.169

AC:

42013

AN:

248794

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.0987

Gnomad EAS exome

AF:

0.257

Gnomad FIN exome

AF:

0.0708

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.141

AC:

204127

AN:

1450576

Hom.:

16147

Cov.:

AF XY:

0.141

AC XY:

102068

AN XY:

721554

show subpopulations

African (AFR)

AF:

0.247

AC:

8201

AN:

33172

American (AMR)

AF:

0.290

AC:

12871

AN:

44398

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2625

AN:

25894

East Asian (EAS)

AF:

0.244

AC:

9566

AN:

39282

South Asian (SAS)

AF:

0.204

AC:

17218

AN:

84552

European-Finnish (FIN)

AF:

0.0750

AC:

3972

AN:

52960

Middle Eastern (MID)

AF:

0.145

AC:

820

AN:

5674

European-Non Finnish (NFE)

AF:

0.127

AC:

139935

AN:

1104848

Other (OTH)

AF:

0.149

AC:

8919

AN:

59796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

7880

15761

23641

31522

39402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5330

10660

15990

21320

26650

<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:

0.171

AC:

25902

AN:

151494

Hom.:

2562

Cov.:

AF XY:

0.169

AC XY:

12500

AN XY:

74046

show subpopulations

African (AFR)

AF:

0.246

AC:

10169

AN:

41390

American (AMR)

AF:

0.221

AC:

3350

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

363

AN:

3462

East Asian (EAS)

AF:

0.257

AC:

1314

AN:

5122

South Asian (SAS)

AF:

0.210

AC:

1013

AN:

4816

European-Finnish (FIN)

AF:

0.0674

AC:

712

AN:

10566

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8520

AN:

67678

Other (OTH)

AF:

0.165

AC:

345

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1068

2137

3205

4274

5342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.142

Hom.:

7139

Bravo

AF:

0.187

Asia WGS

AF:

0.229

AC:

792

AN:

3464

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Immunodeficiency 104 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.3

(source)

DANN

Benign

0.47

PhyloP100

-0.70

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over