rs17612648

chr1-198696788-C-Gchr1-198696788-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.527

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRC	NM_002838.5	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	c.177C>G	p.Pro59=	synonymous_variant	4/33	1	NM_002838.5	A2

Frequencies

GnomAD3 genomes AF: 0.00833 AC: 1268 AN: 152140 Hom.: 8 Cov.: 32

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.: 22 AF XY: 0.00926 AC XY: 1259 AN XY: 135900

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.: 32 AF XY: 0.0128 AC XY: 9340 AN XY: 727144

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.: 8 Cov.: 32 AF XY: 0.00799 AC XY: 595 AN XY: 74432

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.: 0

Bravo AF: 0.00765

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.0143

EpiControl AF: 0.0116

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

PTPRC: BP4, BP7, BS1, BS2 -

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

Invitae

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

Other links and lift over

dbSNP: rs17612648; hg19: chr1-198665917; COSMIC: COSV100723197; COSMIC: COSV100723197;