Genetic Variant PTPN1:c.64-4721G>A (chr20-50556642-G-A) – 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.64-4721G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,048 control chromosomes in the GnomAD database, including 17,512 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 ( 17512 hom., cov: 32)

Consequence

PTPN1
NM_002827.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

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:

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=-1.1).

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.64-4721G>A		intron_variant	Intron 1 of 9	ENST00000371621.5	NP_002818.1	P18031A8K3M3
PTPN1	NM_001278618.2 link	c.-65-8327G>A		intron_variant	Intron 1 of 8		NP_001265547.1	P18031B4DSN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5 link	c.64-4721G>A		intron_variant	Intron 1 of 9	1	NM_002827.4	ENSP00000360683.3		P18031
PTPN1	ENST00000541713.5 link	c.-65-8327G>A		intron_variant	Intron 1 of 8	2		ENSP00000437732.1		B4DSN5

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71649

AN:

151930

Hom.:

17511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.631

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.540

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.502

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

GnomAD4 genome

AF:

0.471

AC:

71669

AN:

152048

Hom.:

17512

Cov.:

AF XY:

0.474

AC XY:

35255

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.325

AC:

13474

AN:

41442

American (AMR)

AF:

0.502

AC:

7670

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

1855

AN:

3468

East Asian (EAS)

AF:

0.631

AC:

3263

AN:

5172

South Asian (SAS)

AF:

0.618

AC:

2980

AN:

4824

European-Finnish (FIN)

AF:

0.540

AC:

5712

AN:

10572

Middle Eastern (MID)

AF:

0.647

AC:

189

AN:

292

European-Non Finnish (NFE)

AF:

0.514

AC:

34932

AN:

67962

Other (OTH)

AF:

0.505

AC:

1066

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1903

3806

5708

7611

9514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.493

Hom.:

47211

Bravo

AF:

0.462

Asia WGS

AF:

0.597

AC:

2075

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.021

(source)

DANN

Benign

0.82

PhyloP100

-1.4

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