Genetic Variant PTPN1:c.1088+535G>T (chr20-50580461-G-T) – 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.1088+535G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,074 control chromosomes in the GnomAD database, including 12,505 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 0.39 ( 12505 hom., cov: 32)

Consequence

PTPN1
NM_002827.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.202

Publications

15 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:

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4 link	c.1088+535G>T		intron_variant	Intron 8 of 9	ENST00000371621.5	NP_002818.1	P18031A8K3M3
PTPN1	NM_001278618.2 link	c.869+535G>T		intron_variant	Intron 7 of 8		NP_001265547.1	P18031B4DSN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5 link	c.1088+535G>T		intron_variant	Intron 8 of 9	1	NM_002827.4	ENSP00000360683.3		P18031
PTPN1	ENST00000541713.5 link	c.869+535G>T		intron_variant	Intron 7 of 8	2		ENSP00000437732.1		B4DSN5

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59611

AN:

151956

Hom.:

12501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.434

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.392

AC:

59632

AN:

152074

Hom.:

12505

Cov.:

AF XY:

0.396

AC XY:

29391

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.224

AC:

9299

AN:

41502

American (AMR)

AF:

0.441

AC:

6742

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1640

AN:

3470

East Asian (EAS)

AF:

0.544

AC:

2817

AN:

5174

South Asian (SAS)

AF:

0.516

AC:

2486

AN:

4822

European-Finnish (FIN)

AF:

0.485

AC:

5109

AN:

10534

Middle Eastern (MID)

AF:

0.579

AC:

169

AN:

292

European-Non Finnish (NFE)

AF:

0.442

AC:

30030

AN:

67964

Other (OTH)

AF:

0.437

AC:

923

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1768

3536

5303

7071

8839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.402

Hom.:

2212

Bravo

AF:

0.384

Asia WGS

AF:

0.479

AC:

1665

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.61

PhyloP100

-0.20

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over