dbSNP rs2206656: PTPN1:c.63+2992C>G (chr20-50513582-C-G) – 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.63+2992C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,990 control chromosomes in the GnomAD database, including 13,949 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 0.42 ( 13949 hom., cov: 32)

Consequence

PTPN1
NM_002827.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.58

Publications

9 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4 link	c.63+2992C>G		intron_variant	Intron 1 of 9	ENST00000371621.5	NP_002818.1	P18031A8K3M3
PTPN1	NM_001278618.2 link	c.-66+2992C>G		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.63+2992C>G		intron_variant	Intron 1 of 9	1	NM_002827.4	ENSP00000360683.3		P18031
PTPN1	ENST00000541713.5 link	c.-66+2992C>G		intron_variant	Intron 1 of 8	2		ENSP00000437732.1		B4DSN5

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64409

AN:

151872

Hom.:

13918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.403

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

GnomAD4 genome

AF:

0.424

AC:

64493

AN:

151990

Hom.:

13949

Cov.:

AF XY:

0.421

AC XY:

31273

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.531

AC:

21998

AN:

41452

American (AMR)

AF:

0.424

AC:

6476

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1306

AN:

3472

East Asian (EAS)

AF:

0.299

AC:

1548

AN:

5172

South Asian (SAS)

AF:

0.337

AC:

1618

AN:

4806

European-Finnish (FIN)

AF:

0.365

AC:

3854

AN:

10566

Middle Eastern (MID)

AF:

0.257

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.390

AC:

26495

AN:

67938

Other (OTH)

AF:

0.401

AC:

843

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1898

3796

5695

7593

9491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.420

Hom.:

1722

Bravo

AF:

0.434

Asia WGS

AF:

0.339

AC:

1179

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

9.3

(source)

DANN

Benign

0.26

PhyloP100

1.6

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