ENST00000359785.10:c.2378C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000359785.10(PTPN22):c.2378C>T(p.Ser793Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,606,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PTPN22
ENST00000359785.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

1 publications found

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:

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

AP4B1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2221539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
PTPN22	NM_015967.8 link	c.2378C>T	p.Ser793Leu	missense_variant	Exon 21 of 21	NP_057051.4	Q9Y2R2B4DZW8
PTPN22	NM_001308297.2 link	c.2306C>T	p.Ser769Leu	missense_variant	Exon 20 of 20	NP_001295226.2	Q9Y2R2G3K0T4
PTPN22	NM_001193431.3 link	c.2294C>T	p.Ser765Leu	missense_variant	Exon 21 of 21	NP_001180360.2	Q9Y2R2-4B4DZW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10 link	c.2378C>T	p.Ser793Leu	missense_variant	Exon 21 of 21	1		ENSP00000352833.5		A0A0B4J1S7

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245640

AF XY:

0.00000754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454800

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723548

show subpopulations

African (AFR)

AF:

0.0000604

AC:

AN:

33120

American (AMR)

AF:

0.00

AC:

AN:

43448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25944

East Asian (EAS)

AF:

0.00

AC:

AN:

39504

South Asian (SAS)

AF:

0.00

AC:

AN:

84304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109298

Other (OTH)

AF:

0.0000333

AC:

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74256

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41404

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000718

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 06, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2378C>T (p.S793L) alteration is located in exon 21 (coding exon 21) of the PTPN22 gene. This alteration results from a C to T substitution at nucleotide position 2378, causing the serine (S) at amino acid position 793 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

.;.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.87

D;D;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.86

PhyloP100

1.7

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

D;.;D

REVEL

Benign

0.098

Sift

Benign

0.043

D;.;D

Sift4G

Benign

0.23

T;T;T

Vest4

0.22

MutPred

0.14

Loss of phosphorylation at S793 (P = 0.029);.;.;

MVP

0.47

MPC

0.095

ClinPred

0.90

GERP RS

4.5

gMVP

0.33

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

ENST00000359785.10:c.2378C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over