20-50575367-T-C

Variant names:

• chr20-50575367-T-C
• rs754118
• NM_002827.4:c.492+713T>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.492+713T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,018 control chromosomes in the GnomAD database, including 29,867 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 (29867 hom., cov: 32)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 20 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

ENSG00000232043 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.492+713T>C		intron_variant	Intron 5 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.273+713T>C		intron_variant	Intron 4 of 8		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.492+713T>C		intron_variant	Intron 5 of 9	1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.273+713T>C		intron_variant	Intron 4 of 8	2		ENSP00000437732.1
ENSG00000232043	ENST00000431019.1	n.549-354A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95282 AN: 151900 Hom.: 29839 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.627 AC: 95357 AN: 152018 Hom.: 29867 Cov.: 32 AF XY: 0.628 AC XY: 46685 AN XY: 74284

African (AFR) AF: 0.598 AC: 24783 AN: 41410

American (AMR) AF: 0.610 AC: 9323 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2262 AN: 3466

East Asian (EAS) AF: 0.682 AC: 3518 AN: 5162

South Asian (SAS) AF: 0.670 AC: 3223 AN: 4814

European-Finnish (FIN) AF: 0.638 AC: 6749 AN: 10582

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.636 AC: 43259 AN: 67978

Other (OTH) AF: 0.648 AC: 1368 AN: 2112

Alfa AF: 0.633 Hom.: 93490

Bravo AF: 0.625

Asia WGS AF: 0.668 AC: 2325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.41
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs754118; hg19: chr20-49191904;