chr1-113852067-C-T

Position:

chr1-113852067-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015967.8(PTPN22):c.788G>A(p.Arg263Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0209 in 1,610,848 control chromosomes in the GnomAD database, including 418 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R263W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.016 ( 30 hom., cov: 32)

Exomes 𝑓: 0.021 ( 388 hom. )

Consequence

PTPN22
NM_015967.8 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.93

Variant links:

Genes affected

PTPN22 (HGNC:9652): (protein tyrosine phosphatase non-receptor type 22) This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves' disease. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Mar 2009]

PTPN22 links:

PTPN22 (HGNC:):

PTPN22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004177779).

BP6

Variant 1-113852067-C-T is Benign according to our data. Variant chr1-113852067-C-T is described in ClinVar as [Benign]. Clinvar id is 3353083.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0162 (2469/152216) while in subpopulation NFE AF= 0.0246 (1672/68006). AF 95% confidence interval is 0.0236. There are 30 homozygotes in gnomad4. There are 1159 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
PTPN22	NM_015967.8 linkuse as main transcript	c.788G>A	p.Arg263Gln	missense_variant	10/21	NP_057051.4	Q9Y2R2B4DZW8
PTPN22	NM_001308297.1 linkuse as main transcript	c.716G>A	p.Arg239Gln	missense_variant	9/20	NP_001295226.2	Q9Y2R2G3K0T4
PTPN22	NM_001193431.2 linkuse as main transcript	c.788G>A	p.Arg263Gln	missense_variant	10/21	NP_001180360.2	Q9Y2R2-4B4DZW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10 linkuse as main transcript	c.788G>A	p.Arg263Gln	missense_variant	10/21	1		ENSP00000352833.5		A0A0B4J1S7

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2471

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0197

GnomAD3 exomes

AF:

0.0171

AC:

4281

AN:

250966

Hom.:

AF XY:

0.0176

AC XY:

2384

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.00475

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0133

Gnomad FIN exome

AF:

0.0223

Gnomad NFE exome

AF:

0.0226

Gnomad OTH exome

AF:

0.0183

GnomAD4 exome

AF:

0.0213

AC:

31131

AN:

1458632

Hom.:

388

Cov.:

AF XY:

0.0209

AC XY:

15178

AN XY:

725736

show subpopulations

Gnomad4 AFR exome

AF:

0.00383

Gnomad4 AMR exome

AF:

0.0147

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0120

Gnomad4 FIN exome

AF:

0.0196

Gnomad4 NFE exome

AF:

0.0241

Gnomad4 OTH exome

AF:

0.0181

GnomAD4 genome

AF:

0.0162

AC:

2469

AN:

152216

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1159

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00994

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0223

Hom.:

Bravo

AF:

0.0151

TwinsUK

AF:

0.0240

AC:

ALSPAC

AF:

0.0306

AC:

118

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.0210

AC:

181

ExAC

AF:

0.0169

AC:

2049

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0228

EpiControl

AF:

0.0211

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTPN22-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.047

.;.;.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.60

T;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.38

PROVEAN

Benign

2.6

N;.;N;N

REVEL

Benign

0.20

Sift

Benign

1.0

T;.;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010

.;.;B;.

Vest4

0.17

MPC

0.083

ClinPred

0.0090

GERP RS

3.4

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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