20-50516532-A-G

Variant names:

• chr20-50516532-A-G
• rs932420
• NM_002827.4:c.63+5942A>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+5942A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,050 control chromosomes in the GnomAD database, including 21,167 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 0.52 (21167 hom., cov: 33)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.710
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 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+5942A>G		intron	N/A	NP_002818.1
	PTPN1	NM_001278618.2		c.-66+5942A>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+5942A>G		intron	N/A	ENSP00000360683.3
	PTPN1	ENST00000541713.5	TSL:2	c.-66+5942A>G		intron	N/A	ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78852 AN: 151930 Hom.: 21128 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.519 AC: 78950 AN: 152050 Hom.: 21167 Cov.: 33 AF XY: 0.515 AC XY: 38300 AN XY: 74308

African (AFR) AF: 0.667 AC: 27643 AN: 41452

American (AMR) AF: 0.489 AC: 7477 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1662 AN: 5180

South Asian (SAS) AF: 0.371 AC: 1792 AN: 4824

European-Finnish (FIN) AF: 0.448 AC: 4733 AN: 10570

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32500 AN: 67962

Other (OTH) AF: 0.489 AC: 1031 AN: 2110

Alfa AF: 0.487 Hom.: 34894

Bravo AF: 0.530

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.69
PhyloP100		0.71
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: rs932420; hg19: chr20-49133069;