chr1-113830008-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000359785.10(PTPN22):c.2075C>G(p.Ser692Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,605,180 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0023 ( 12 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 49 hom. )
Consequence
PTPN22
ENST00000359785.10 missense
ENST00000359785.10 missense
Scores
2
4
10
Clinical Significance
Conservation
PhyloP100: 2.46
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0045930743).
BP6
?
Variant 1-113830008-G-C is Benign according to our data. Variant chr1-113830008-G-C is described in ClinVar as [Benign]. Clinvar id is 773112.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00228 (347/152246) while in subpopulation AMR AF= 0.0194 (297/15302). AF 95% confidence interval is 0.0176. There are 12 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN22 | NM_015967.8 | c.2075C>G | p.Ser692Cys | missense_variant | 17/21 | ENST00000359785.10 | |
PTPN22 | XM_047417630.1 | c.1925C>G | p.Ser642Cys | missense_variant | 15/19 | ||
AP4B1-AS1 | NR_125965.1 | n.414+14536G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN22 | ENST00000359785.10 | c.2075C>G | p.Ser692Cys | missense_variant | 17/21 | 1 | NM_015967.8 | P1 | |
ENST00000664434.1 | n.419-1754G>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00224 AC: 341AN: 152128Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00572 AC: 1433AN: 250528Hom.: 31 AF XY: 0.00433 AC XY: 586AN XY: 135468
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GnomAD4 exome AF: 0.00147 AC: 2141AN: 1452934Hom.: 49 Cov.: 30 AF XY: 0.00133 AC XY: 962AN XY: 723326
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GnomAD4 genome ? AF: 0.00228 AC: 347AN: 152246Hom.: 12 Cov.: 32 AF XY: 0.00251 AC XY: 187AN XY: 74444
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D;D;N
REVEL
Benign
Sift
Benign
D;.;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
1.0
.;.;.;D;.
Vest4
MVP
MPC
ClinPred
T
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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