20-50578329-A-AT

Variant names:

• chr20-50578329-A-AT
• rs3215684
• NM_002827.4:c.493-91_493-90insT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002827.4(PTPN1):​c.493-91_493-90insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,080,034 control chromosomes in the GnomAD database, including 222,650 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (29647 hom., cov: 0)
  • Exomes 𝑓: 0.64 (193003 hom.)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 9 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 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.493-91_493-90insT		intron	N/A	NP_002818.1	A8K3M3
	PTPN1	NM_001278618.2		c.274-91_274-90insT		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.493-91_493-90insT		intron	N/A	ENSP00000360683.3	P18031
	PTPN1	ENST00000859846.1		c.493-91_493-90insT		intron	N/A	ENSP00000529905.1
	PTPN1	ENST00000859845.1		c.493-839_493-838insT		intron	N/A	ENSP00000529904.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94922 AN: 151842 Hom.: 29624 Cov.: 0

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.643 AC: 596431 AN: 928074 Hom.: 193003 AF XY: 0.644 AC XY: 307073 AN XY: 476748

African (AFR) AF: 0.589 AC: 13310 AN: 22586

American (AMR) AF: 0.588 AC: 23331 AN: 39680

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 12858 AN: 19800

East Asian (EAS) AF: 0.711 AC: 26372 AN: 37094

South Asian (SAS) AF: 0.678 AC: 45739 AN: 67438

European-Finnish (FIN) AF: 0.646 AC: 28490 AN: 44078

Middle Eastern (MID) AF: 0.688 AC: 3168 AN: 4606

European-Non Finnish (NFE) AF: 0.639 AC: 415709 AN: 650310

Other (OTH) AF: 0.646 AC: 27454 AN: 42482

GnomAD4 genome AF: 0.625 AC: 94990 AN: 151960 Hom.: 29647 Cov.: 0 AF XY: 0.626 AC XY: 46507 AN XY: 74264

African (AFR) AF: 0.590 AC: 24453 AN: 41422

American (AMR) AF: 0.607 AC: 9280 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2266 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3548 AN: 5150

South Asian (SAS) AF: 0.673 AC: 3247 AN: 4824

European-Finnish (FIN) AF: 0.638 AC: 6736 AN: 10558

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.636 AC: 43235 AN: 67938

Other (OTH) AF: 0.639 AC: 1348 AN: 2108

Alfa AF: 0.623 Hom.: 3611

Bravo AF: 0.623

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.058
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: rs3215684; hg19: chr20-49194866; COSMIC: COSV65407183; COSMIC: COSV65407183;