20-50579630-T-C

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.397
Variant links:
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
PTPN1NM_002827.4 linkuse as main transcriptc.865-73T>C intron_variant ENST00000371621.5
PTPN1NM_001278618.2 linkuse as main transcriptc.646-73T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTPN1ENST00000371621.5 linkuse as main transcriptc.865-73T>C intron_variant 1 NM_002827.4 P1
PTPN1ENST00000541713.5 linkuse as main transcriptc.646-73T>C intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.620
AC:
94198
AN:
151926
Hom.:
29220
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.573
Gnomad AMI
AF:
0.712
Gnomad AMR
AF:
0.608
Gnomad ASJ
AF:
0.652
Gnomad EAS
AF:
0.681
Gnomad SAS
AF:
0.669
Gnomad FIN
AF:
0.640
Gnomad MID
AF:
0.763
Gnomad NFE
AF:
0.636
Gnomad OTH
AF:
0.641
GnomAD4 exome
AF:
0.645
AC:
764082
AN:
1185540
Hom.:
247154
AF XY:
0.645
AC XY:
385808
AN XY:
597764
show subpopulations
Gnomad4 AFR exome
AF:
0.576
Gnomad4 AMR exome
AF:
0.588
Gnomad4 ASJ exome
AF:
0.648
Gnomad4 EAS exome
AF:
0.696
Gnomad4 SAS exome
AF:
0.675
Gnomad4 FIN exome
AF:
0.648
Gnomad4 NFE exome
AF:
0.644
Gnomad4 OTH exome
AF:
0.649
GnomAD4 genome
AF:
0.620
AC:
94271
AN:
152044
Hom.:
29247
Cov.:
32
AF XY:
0.621
AC XY:
46178
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.573
Gnomad4 AMR
AF:
0.607
Gnomad4 ASJ
AF:
0.652
Gnomad4 EAS
AF:
0.680
Gnomad4 SAS
AF:
0.670
Gnomad4 FIN
AF:
0.640
Gnomad4 NFE
AF:
0.636
Gnomad4 OTH
AF:
0.645
Alfa
AF:
0.629
Hom.:
8026
Bravo
AF:
0.616
Asia WGS
AF:
0.666
AC:
2318
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.2
DANN
Benign
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2282147; hg19: chr20-49196167; API