Variant chr1-113834946-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000359785.10(PTPN22):c.1858T>C(p.Trp620Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,574,936 control chromosomes in the GnomAD database, including 658,157 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 Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.93 ( 66570 hom., cov: 31)

Exomes 𝑓: 0.91 ( 591587 hom. )

Consequence

PTPN22
ENST00000359785.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.807

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.5175065E-7).

BP6

Variant 1-113834946-A-G is Benign according to our data. Variant chr1-113834946-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PTPN22	NM_015967.8 linkuse as main transcript	c.1858T>C	p.Trp620Arg	missense_variant	14/21	ENST00000359785.10	NP_057051.4
PTPN22	XM_047417630.1 linkuse as main transcript	c.1708T>C	p.Trp570Arg	missense_variant	12/19		XP_047273586.1
AP4B1-AS1	NR_125965.1 linkuse as main transcript	n.414+19474A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10 linkuse as main transcript	c.1858T>C	p.Trp620Arg	missense_variant	14/21	1	NM_015967.8	ENSP00000352833	P1
	ENST00000664434.1 linkuse as main transcript	n.470+3133A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.934

AC:

142065

AN:

152082

Hom.:

66511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.985

Gnomad AMI

AF:

0.961

Gnomad AMR

AF:

0.961

Gnomad ASJ

AF:

0.944

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.988

Gnomad FIN

AF:

0.853

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.900

Gnomad OTH

AF:

0.946

GnomAD3 exomes

AF:

0.929

AC:

203641

AN:

219224

Hom.:

94842

AF XY:

0.930

AC XY:

111378

AN XY:

119762

show subpopulations

Gnomad AFR exome

AF:

0.986

Gnomad AMR exome

AF:

0.969

Gnomad ASJ exome

AF:

0.949

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.987

Gnomad FIN exome

AF:

0.851

Gnomad NFE exome

AF:

0.901

Gnomad OTH exome

AF:

0.928

GnomAD4 exome

AF:

0.911

AC:

1296378

AN:

1422736

Hom.:

591587

Cov.:

AF XY:

0.913

AC XY:

646370

AN XY:

707954

show subpopulations

Gnomad4 AFR exome

AF:

0.987

Gnomad4 AMR exome

AF:

0.967

Gnomad4 ASJ exome

AF:

0.952

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.985

Gnomad4 FIN exome

AF:

0.855

Gnomad4 NFE exome

AF:

0.899

Gnomad4 OTH exome

AF:

0.928

GnomAD4 genome

AF:

0.934

AC:

142183

AN:

152200

Hom.:

66570

Cov.:

AF XY:

0.935

AC XY:

69589

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.985

Gnomad4 AMR

AF:

0.961

Gnomad4 ASJ

AF:

0.944

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.987

Gnomad4 FIN

AF:

0.853

Gnomad4 NFE

AF:

0.900

Gnomad4 OTH

AF:

0.946

Alfa

AF:

0.915

Hom.:

140296

Bravo

AF:

0.944

TwinsUK

AF:

0.897

AC:

3327

ALSPAC

AF:

0.899

AC:

3465

ESP6500AA

AF:

0.982

AC:

4326

ESP6500EA

AF:

0.906

AC:

7791

ExAC

AF:

0.933

AC:

113294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.020

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0026

.;.;T;.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.025

T;T;T;T;T

MetaRNN

Benign

5.5e-7

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

5.1

N;.;N;N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;.;.;B;.

Vest4

0.13

MutPred

0.37

Gain of disorder (P = 6e-04);.;.;Gain of disorder (P = 6e-04);.;

MPC

0.13

ClinPred

0.0017

GERP RS

2.7

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over