20-50579630-T-C
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002827.4(PTPN1):c.865-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,337,584 control chromosomes in the GnomAD database, including 276,401 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: 𝑓 0.62 ( 29247 hom., cov: 32)
Exomes 𝑓: 0.64 ( 247154 hom. )
Consequence
PTPN1
NM_002827.4 intron
NM_002827.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.397
Genes affected
PTPN1 (HGNC:9642): (protein tyrosine phosphatase non-receptor type 1) The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN1 | NM_002827.4 | c.865-73T>C | intron_variant | ENST00000371621.5 | |||
PTPN1 | NM_001278618.2 | c.646-73T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN1 | ENST00000371621.5 | c.865-73T>C | intron_variant | 1 | NM_002827.4 | P1 | |||
PTPN1 | ENST00000541713.5 | c.646-73T>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.620 AC: 94198AN: 151926Hom.: 29220 Cov.: 32
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GnomAD4 exome AF: 0.645 AC: 764082AN: 1185540Hom.: 247154 AF XY: 0.645 AC XY: 385808AN XY: 597764
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GnomAD4 genome AF: 0.620 AC: 94271AN: 152044Hom.: 29247 Cov.: 32 AF XY: 0.621 AC XY: 46178AN XY: 74310
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at