Variant 20-50582818-C-CG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002827.4(PTPN1):c.*104dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,430,574 control chromosomes in the GnomAD database, including 3,488 homozygotes. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.050 ( 270 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3218 hom. )

Consequence

PTPN1
NM_002827.4 3_prime_UTR

Scores

Not classified

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -1.70

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]

PTPN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN1	NM_002827.4 linkuse as main transcript	c.*104dup		3_prime_UTR_variant	10/10	ENST00000371621.5
PTPN1	NM_001278618.2 linkuse as main transcript	c.*104dup		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN1	ENST00000371621.5 linkuse as main transcript	c.*104dup		3_prime_UTR_variant	10/10	1	NM_002827.4	P1
PTPN1	ENST00000541713.5 linkuse as main transcript	c.*104dup		3_prime_UTR_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7621

AN:

152178

Hom.:

270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0670

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0759

Gnomad OTH

AF:

0.0507

GnomAD4 exome

AF:

0.0671

AC:

85831

AN:

1278278

Hom.:

3218

Cov.:

AF XY:

0.0658

AC XY:

42034

AN XY:

639138

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.0302

Gnomad4 ASJ exome

AF:

0.0557

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0201

Gnomad4 FIN exome

AF:

0.0690

Gnomad4 NFE exome

AF:

0.0773

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0500

AC:

7621

AN:

152296

Hom.:

270

Cov.:

AF XY:

0.0498

AC XY:

3706

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.0459

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0172

Gnomad4 FIN

AF:

0.0670

Gnomad4 NFE

AF:

0.0759

Gnomad4 OTH

AF:

0.0507

Alfa

AF:

0.0191

Hom.:

Bravo

AF:

0.0468

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Insulin resistance, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over