Genetic Variant PTPN1:c.355-522T>C (chr20-50573995-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002827.4(PTPN1):c.355-522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,332 control chromosomes in the GnomAD database, including 42,887 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 0.75 ( 42830 hom., cov: 33)

Exomes 𝑓: 0.74 ( 57 hom. )

Consequence

PTPN1
NM_002827.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0220

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

autoinflammatory syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

PTPN1 links:

ENSG00000232043 (HGNC:):

ENSG00000232043 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4 link	c.355-522T>C		intron_variant	Intron 4 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2 link	c.136-522T>C		intron_variant	Intron 3 of 8		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PTPN1	ENST00000371621.5 link	c.355-522T>C	intron_variant	Intron 4 of 9	1	NM_002827.4	ENSP00000360683.3
ENSG00000232043	ENST00000431019.1 link	n.1567A>G	non_coding_transcript_exon_variant	Exon 2 of 2	2
PTPN1	ENST00000541713.5 link	c.136-522T>C	intron_variant	Intron 3 of 8	2		ENSP00000437732.1

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113919

AN:

152018

Hom.:

42785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.776

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.865

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.723

Gnomad OTH

AF:

0.744

GnomAD4 exome

AF:

0.740

AC:

145

AN:

196

Hom.:

Cov.:

AF XY:

0.792

AC XY:

AN XY:

106

show subpopulations

African (AFR)

AF:

0.813

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.600

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.735

AC:

100

AN:

136

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.749

AC:

114013

AN:

152136

Hom.:

42830

Cov.:

AF XY:

0.754

AC XY:

56079

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.784

AC:

32559

AN:

41512

American (AMR)

AF:

0.677

AC:

10352

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

2476

AN:

3470

East Asian (EAS)

AF:

0.906

AC:

4680

AN:

5166

South Asian (SAS)

AF:

0.866

AC:

4174

AN:

4822

European-Finnish (FIN)

AF:

0.765

AC:

8096

AN:

10582

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.723

AC:

49148

AN:

67980

Other (OTH)

AF:

0.746

AC:

1576

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1495

2991

4486

5982

7477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.730

Hom.:

126095

Bravo

AF:

0.742

Asia WGS

AF:

0.873

AC:

3038

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.8

(source)

DANN

Benign

0.82

PhyloP100

-0.022

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over