20-50568886-C-T

Variant names:

• chr20-50568886-C-T
• rs3787345
• NM_002827.4:c.354+408C>T

Variant summary

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

The NM_002827.4(PTPN1):​c.354+408C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,944 control chromosomes in the GnomAD database, including 25,503 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 0.58 (25503 hom., cov: 31)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 14 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.354+408C>T		intron_variant	Intron 4 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.135+408C>T		intron_variant	Intron 3 of 8		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.354+408C>T		intron_variant	Intron 4 of 9	1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.135+408C>T		intron_variant	Intron 3 of 8	2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87997 AN: 151826 Hom.: 25491 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.579 AC: 88047 AN: 151944 Hom.: 25503 Cov.: 31 AF XY: 0.583 AC XY: 43255 AN XY: 74244

African (AFR) AF: 0.534 AC: 22079 AN: 41380

American (AMR) AF: 0.572 AC: 8740 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3238 AN: 5160

South Asian (SAS) AF: 0.636 AC: 3061 AN: 4812

European-Finnish (FIN) AF: 0.621 AC: 6566 AN: 10576

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40143 AN: 67962

Other (OTH) AF: 0.601 AC: 1265 AN: 2106

Alfa AF: 0.459 Hom.: 1337

Bravo AF: 0.574

Asia WGS AF: 0.624 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.68
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3787345; hg19: chr20-49185423;