Variant 1-113829641-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015967.8(PTPN22):c.2201C>T(p.Ser734Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,492 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTPN22
NM_015967.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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:

ENSG00000231128 (HGNC:):

ENSG00000231128 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3365775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
PTPN22	NM_015967.8 linkuse as main transcript	c.2201C>T	p.Ser734Phe	missense_variant	18/21	NP_057051.4	Q9Y2R2B4DZW8
PTPN22	NM_001308297.1 linkuse as main transcript	c.2129C>T	p.Ser710Phe	missense_variant	17/20	NP_001295226.2	Q9Y2R2G3K0T4
PTPN22	NM_001193431.2 linkuse as main transcript	c.2117C>T	p.Ser706Phe	missense_variant	18/21	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.2201C>T	p.Ser734Phe	missense_variant	18/21	1		ENSP00000352833.5		A0A0B4J1S7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458492

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Aug 16, 2022

PP3, PM2_SUP -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;.;T;.;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.34

T;T;T;T;T

MetaSVM

Benign

-0.74

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.1

D;.;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0010

D;.;D;D;D

Sift4G

Uncertain

0.010

D;D;D;T;T

Polyphen

1.0

.;.;.;D;.

Vest4

0.34

MutPred

0.14

Loss of phosphorylation at S734 (P = 0.0455);.;.;Loss of phosphorylation at S734 (P = 0.0455);.;

MVP

0.58

MPC

0.43

ClinPred

0.99

GERP RS

5.5

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over