rs17612648

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002838.5(PTPRC):c.177C>G(p.Pro59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,926 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P59P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0083 ( 8 hom., cov: 32)

Exomes 𝑓: 0.013 ( 169 hom. )

Consequence

PTPRC
NM_002838.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.527

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-198696788-C-G is Benign according to our data. Variant chr1-198696788-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 378444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.527 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00833 (1268/152258) while in subpopulation NFE AF= 0.0138 (937/68020). AF 95% confidence interval is 0.013. There are 8 homozygotes in gnomad4. There are 595 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRC	NM_002838.5 linkuse as main transcript	c.177C>G	p.Pro59=	synonymous_variant	4/33	ENST00000442510.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRC	ENST00000442510.8 linkuse as main transcript	c.177C>G	p.Pro59=	synonymous_variant	4/33	1	NM_002838.5	A2	P08575-3

Frequencies

GnomAD3 genomes

AF:

0.00833

AC:

1268

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00877

AC:

2205

AN:

251456

Hom.:

AF XY:

0.00926

AC XY:

1259

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.00448

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.0127

AC:

18551

AN:

1461668

Hom.:

169

Cov.:

AF XY:

0.0128

AC XY:

9340

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.00537

Gnomad4 NFE exome

AF:

0.0147

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.00833

AC:

1268

AN:

152258

Hom.:

Cov.:

AF XY:

0.00799

AC XY:

595

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00258

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00726

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.00765

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0143

EpiControl

AF:

0.0116

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	PTPRC: BP4, BP7, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2015

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. -

Immunodeficiency 105

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

PTPRC POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jun 03, 2011

- -

Immunodeficiency 104

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.4

DANN

Benign

0.62

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