20-50536246-A-G

Variant names:

• chr20-50536246-A-G
• rs6067484
• NM_002827.4:c.64-25117A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002827.4(PTPN1):​c.64-25117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,210 control chromosomes in the GnomAD database, including 3,709 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 0.20 (3709 hom., cov: 32)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 16 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002827.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	NM_002827.4	MANE Select	c.64-25117A>G		intron	N/A	NP_002818.1	A8K3M3
	PTPN1	NM_001278618.2		c.-66+25656A>G		intron	N/A	NP_001265547.1	B4DSN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	ENST00000371621.5	TSL:1 MANE Select	c.64-25117A>G		intron	N/A	ENSP00000360683.3	P18031
	PTPN1	ENST00000859846.1		c.64-25117A>G		intron	N/A	ENSP00000529905.1
	PTPN1	ENST00000859845.1		c.64-25117A>G		intron	N/A	ENSP00000529904.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30180 AN: 152092 Hom.: 3702 Cov.: 32

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.198 AC: 30185 AN: 152210 Hom.: 3709 Cov.: 32 AF XY: 0.197 AC XY: 14644 AN XY: 74408

African (AFR) AF: 0.0484 AC: 2010 AN: 41556

American (AMR) AF: 0.303 AC: 4638 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3468

East Asian (EAS) AF: 0.0935 AC: 485 AN: 5188

South Asian (SAS) AF: 0.132 AC: 637 AN: 4828

European-Finnish (FIN) AF: 0.235 AC: 2492 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18223 AN: 67982

Other (OTH) AF: 0.216 AC: 456 AN: 2110

Alfa AF: 0.230 Hom.: 589

Bravo AF: 0.200

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.38
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6067484; hg19: chr20-49152783;