chr20-50579743-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_002827.4(PTPN1):​c.905C>T​(p.Pro302Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PTPN1
NM_002827.4 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09353405).
BP6
Variant 20-50579743-C-T is Benign according to our data. Variant chr20-50579743-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652394.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTPN1NM_002827.4 linkuse as main transcriptc.905C>T p.Pro302Leu missense_variant 8/10 ENST00000371621.5
PTPN1NM_001278618.2 linkuse as main transcriptc.686C>T p.Pro229Leu missense_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTPN1ENST00000371621.5 linkuse as main transcriptc.905C>T p.Pro302Leu missense_variant 8/101 NM_002827.4 P1
PTPN1ENST00000541713.5 linkuse as main transcriptc.686C>T p.Pro229Leu missense_variant 7/92

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251350
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460812
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
726678
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2022PTPN1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Benign
0.0096
T;T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.065
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.16
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.094
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.43
N;N
REVEL
Benign
0.11
Sift
Benign
0.20
T;T
Sift4G
Benign
0.28
T;T
Polyphen
0.0
.;B
Vest4
0.23
MutPred
0.25
.;Loss of glycosylation at P302 (P = 0.0166);
MVP
0.082
MPC
0.92
ClinPred
0.23
T
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.057
gMVP
0.58

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: rs749433251; hg19: chr20-49196280; API