rs74163663
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015967.8(PTPN22):āc.2242A>Gā(p.Arg748Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,586,510 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.00041 ( 0 hom., cov: 32)
Exomes š: 0.00056 ( 1 hom. )
Consequence
PTPN22
NM_015967.8 missense
NM_015967.8 missense
Scores
1
8
9
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.92
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.047892004).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPN22 | NM_015967.8 | c.2242A>G | p.Arg748Gly | missense_variant | 18/21 | NP_057051.4 | ||
PTPN22 | NM_001308297.1 | c.2170A>G | p.Arg724Gly | missense_variant | 17/20 | NP_001295226.2 | ||
PTPN22 | NM_001193431.2 | c.2158A>G | p.Arg720Gly | missense_variant | 18/21 | NP_001180360.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPN22 | ENST00000359785.10 | c.2242A>G | p.Arg748Gly | missense_variant | 18/21 | 1 | ENSP00000352833.5 |
Frequencies
GnomAD3 genomes AF: 0.000414 AC: 63AN: 152102Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000645 AC: 157AN: 243374Hom.: 1 AF XY: 0.000538 AC XY: 71AN XY: 131978
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GnomAD4 exome AF: 0.000560 AC: 803AN: 1434290Hom.: 1 Cov.: 28 AF XY: 0.000509 AC XY: 364AN XY: 714946
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GnomAD4 genome AF: 0.000414 AC: 63AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29AN XY: 74442
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
1.0
.;.;.;D;.
Vest4
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at