chr20-50521512-A-G

Variant names:

• chr20-50521512-A-G
• rs2426157
• NM_002827.4:c.63+10922A>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.63+10922A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,172 control chromosomes in the GnomAD database, including 4,830 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 0.25 (4830 hom., cov: 33)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 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.63+10922A>G		intron	N/A	NP_002818.1
	PTPN1	NM_001278618.2		c.-66+10922A>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.63+10922A>G		intron	N/A	ENSP00000360683.3
	PTPN1	ENST00000541713.5	TSL:2	c.-66+10922A>G		intron	N/A	ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38129 AN: 152052 Hom.: 4822 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.251 AC: 38155 AN: 152172 Hom.: 4830 Cov.: 33 AF XY: 0.247 AC XY: 18379 AN XY: 74400

African (AFR) AF: 0.209 AC: 8689 AN: 41502

American (AMR) AF: 0.325 AC: 4977 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1007 AN: 3470

East Asian (EAS) AF: 0.150 AC: 779 AN: 5182

South Asian (SAS) AF: 0.141 AC: 680 AN: 4832

European-Finnish (FIN) AF: 0.244 AC: 2584 AN: 10590

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18634 AN: 67982

Other (OTH) AF: 0.260 AC: 549 AN: 2114

Alfa AF: 0.271 Hom.: 9844

Bravo AF: 0.258

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.70
PhyloP100		-3.0
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: rs2426157; hg19: chr20-49138049;