rs41314043

chr1-198708257-G-A

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.1029G>A(p.Gln343=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.447

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=-0.91).
• BP6: Variant 1-198708257-G-A is Benign according to our data. Variant chr1-198708257-G-A is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRC	NM_002838.5	c.1029G>A	p.Gln343=	synonymous_variant	10/33	ENST00000442510.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRC	ENST00000442510.8	c.1029G>A	p.Gln343=	synonymous_variant	10/33	1	NM_002838.5	A2

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2136 AN: 152140 Hom.: 25 Cov.: 33

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

GnomAD3 exomes AF: 0.0150 AC: 3757 AN: 250326 Hom.: 53 AF XY: 0.0155 AC XY: 2096 AN XY: 135548

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 SAS exome AF: 0.0117

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.: 30 AF XY: 0.0159 AC XY: 11467 AN XY: 722920

Gnomad4 AFR exome AF: 0.00505

Gnomad4 AMR exome AF: 0.00761

Gnomad4 ASJ exome AF: 0.0180

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.0474

Gnomad4 NFE exome AF: 0.0160

Gnomad4 OTH exome AF: 0.0150

GnomAD4 genome AF: 0.0141 AC: 2142 AN: 152258 Hom.: 25 Cov.: 33 AF XY: 0.0152 AC XY: 1133 AN XY: 74438

Gnomad4 AFR AF: 0.00522

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0493

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0145 Hom.: 11

Bravo AF: 0.0105

Asia WGS AF: 0.00579 AC: 21 AN: 3470

EpiCase AF: 0.0169

EpiControl AF: 0.0149

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 02, 2013

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 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	-0.91
Cadd	Benign	0.15
Dann	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs41314043; hg19: chr1-198677386;