NM_002827.4:c.64-11189T>C

Variant names:

• chr20-50550174-T-C
• rs1570179
• NM_002827.4:c.64-11189T>C

Variant summary

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

The NM_002827.4(PTPN1):​c.64-11189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,974 control chromosomes in the GnomAD database, including 29,969 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 0.63 (29969 hom., cov: 31)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 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.64-11189T>C		intron	N/A	NP_002818.1
	PTPN1	NM_001278618.2		c.-65-14795T>C		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.64-11189T>C		intron	N/A	ENSP00000360683.3
	PTPN1	ENST00000541713.5	TSL:2	c.-65-14795T>C		intron	N/A	ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95444 AN: 151856 Hom.: 29942 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.629 AC: 95519 AN: 151974 Hom.: 29969 Cov.: 31 AF XY: 0.630 AC XY: 46770 AN XY: 74258

African (AFR) AF: 0.600 AC: 24871 AN: 41424

American (AMR) AF: 0.613 AC: 9362 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2264 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3470 AN: 5174

South Asian (SAS) AF: 0.668 AC: 3219 AN: 4816

European-Finnish (FIN) AF: 0.639 AC: 6733 AN: 10544

Middle Eastern (MID) AF: 0.779 AC: 226 AN: 290

European-Non Finnish (NFE) AF: 0.638 AC: 43356 AN: 67950

Other (OTH) AF: 0.649 AC: 1369 AN: 2110

Alfa AF: 0.623 Hom.: 4778

Bravo AF: 0.626

Asia WGS AF: 0.666 AC: 2317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		0.029
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1570179; hg19: chr20-49166711;