chr1-198702524-A-G

Position:

chr1-198702524-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002838.5(PTPRC):c.577A>G(p.Thr193Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,614,082 control chromosomes in the GnomAD database, including 1,595 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict 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. T193T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.020 ( 177 hom., cov: 32)

Exomes 𝑓: 0.018 ( 1418 hom. )

Consequence

PTPRC
NM_002838.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.56

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.523464E-4).

BP6

Variant 1-198702524-A-G is Benign according to our data. Variant chr1-198702524-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 464444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRC	NM_002838.5 link	c.577A>G	p.Thr193Ala	missense_variant	6/33	ENST00000442510.8	NP_002829.3	P08575-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRC	ENST00000442510.8 link	c.577A>G	p.Thr193Ala	missense_variant	6/33	1	NM_002838.5	ENSP00000411355.3		P08575-3

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3117

AN:

152078

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00536

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0600

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00784

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0430

AC:

10805

AN:

251468

Hom.:

722

AF XY:

0.0388

AC XY:

5279

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.0459

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00854

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0185

AC:

26987

AN:

1461886

Hom.:

1418

Cov.:

AF XY:

0.0188

AC XY:

13696

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00364

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.00562

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.0446

Gnomad4 FIN exome

AF:

0.00165

Gnomad4 NFE exome

AF:

0.00730

Gnomad4 OTH exome

AF:

0.0259

GnomAD4 genome

AF:

0.0205

AC:

3120

AN:

152196

Hom.:

177

Cov.:

AF XY:

0.0223

AC XY:

1658

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00535

Gnomad4 AMR

AF:

0.0602

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.193

Gnomad4 SAS

AF:

0.0496

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00782

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0177

Hom.:

312

Bravo

AF:

0.0277

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.0393

AC:

4772

Asia WGS

AF:

0.134

AC:

464

AN:

3478

EpiCase

AF:

0.00802

EpiControl

AF:

0.00948

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 12716971, 16538473, 15333587) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Dec 10, 2021

- -

Immunodeficiency 105

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 08, 2023

- -

Immunodeficiency 104

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0070

DANN

Benign

0.37

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.00085

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.22

REVEL

Benign

0.069

Sift4G

Benign

0.27

T;T

Vest4

0.0070

MPC

0.17

ClinPred

0.0043

GERP RS

-12

Varity_R

0.043

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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