20-50546698-A-G

Variant names:

• chr20-50546698-A-G
• rs941798
• NM_002827.4:c.64-14665A>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.64-14665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,088 control chromosomes in the GnomAD database, including 12,998 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 0.40 (12998 hom., cov: 32)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 21 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	NM_002827.4	MANE Select	c.64-14665A>G		intron	N/A	NP_002818.1
	PTPN1	NM_001278618.2		c.-65-18271A>G		intron	N/A	NP_001265547.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	ENST00000371621.5	TSL:1 MANE Select	c.64-14665A>G		intron	N/A	ENSP00000360683.3
	PTPN1	ENST00000541713.5	TSL:2	c.-65-18271A>G		intron	N/A	ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61389 AN: 151970 Hom.: 12993 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.404 AC: 61414 AN: 152088 Hom.: 12998 Cov.: 32 AF XY: 0.406 AC XY: 30203 AN XY: 74326

African (AFR) AF: 0.257 AC: 10648 AN: 41494

American (AMR) AF: 0.448 AC: 6844 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3468

East Asian (EAS) AF: 0.546 AC: 2821 AN: 5170

South Asian (SAS) AF: 0.518 AC: 2497 AN: 4822

European-Finnish (FIN) AF: 0.486 AC: 5137 AN: 10564

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30264 AN: 67968

Other (OTH) AF: 0.446 AC: 943 AN: 2114

Alfa AF: 0.436 Hom.: 63327

Bravo AF: 0.397

Asia WGS AF: 0.482 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.2
DANN	Benign	0.84
PhyloP100		-0.20
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: rs941798; hg19: chr20-49163235;