Genetic Variant PTPN1:c.492+37A>C (chr20-50574691-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002827.4(PTPN1):c.492+37A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,564,756 control chromosomes in the GnomAD database, including 213,858 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 0.47 ( 17640 hom., cov: 33)

Exomes 𝑓: 0.52 ( 196218 hom. )

Consequence

PTPN1
NM_002827.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

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:

ENSG00000232043 (HGNC:):

ENSG00000232043 links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4 link	c.492+37A>C		intron_variant	Intron 5 of 9	ENST00000371621.5	NP_002818.1	P18031A8K3M3
PTPN1	NM_001278618.2 link	c.273+37A>C		intron_variant	Intron 4 of 8		NP_001265547.1	P18031B4DSN5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPN1	ENST00000371621.5 link	c.492+37A>C	intron_variant	Intron 5 of 9	1	NM_002827.4	ENSP00000360683.3	P18031
PTPN1	ENST00000541713.5 link	c.273+37A>C	intron_variant	Intron 4 of 8	2		ENSP00000437732.1	B4DSN5
ENSG00000232043	ENST00000431019.1 link	n.871T>G	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

72064

AN:

151972

Hom.:

17640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.631

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.540

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.504

GnomAD3 exomes

AF:

0.529

AC:

109113

AN:

206354

Hom.:

29500

AF XY:

0.536

AC XY:

60494

AN XY:

112954

show subpopulations

Gnomad AFR exome

AF:

0.325

Gnomad AMR exome

AF:

0.521

Gnomad ASJ exome

AF:

0.526

Gnomad EAS exome

AF:

0.619

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.518

Gnomad OTH exome

AF:

0.541

GnomAD4 exome

AF:

0.524

AC:

740865

AN:

1412666

Hom.:

196218

Cov.:

AF XY:

0.528

AC XY:

370836

AN XY:

702978

show subpopulations

Gnomad4 AFR exome

AF:

0.326

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.627

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.518

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.474

AC:

72083

AN:

152090

Hom.:

17640

Cov.:

AF XY:

0.477

AC XY:

35449

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.334

Gnomad4 AMR

AF:

0.504

Gnomad4 ASJ

AF:

0.535

Gnomad4 EAS

AF:

0.631

Gnomad4 SAS

AF:

0.617

Gnomad4 FIN

AF:

0.540

Gnomad4 NFE

AF:

0.514

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.421

Hom.:

2425

Bravo

AF:

0.466

Asia WGS

AF:

0.597

AC:

2076

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.035

DANN

Benign

0.61

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over