20-50580461-G-T

Variant names:

• chr20-50580461-G-T
• rs3787348
• NM_002827.4:c.1088+535G>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.1088+535G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,074 control chromosomes in the GnomAD database, including 12,505 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 0.39 (12505 hom., cov: 32)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.1088+535G>T		intron_variant	Intron 8 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.869+535G>T		intron_variant	Intron 7 of 8		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.1088+535G>T		intron_variant	Intron 8 of 9	1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.869+535G>T		intron_variant	Intron 7 of 8	2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59611 AN: 151956 Hom.: 12501 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.392 AC: 59632 AN: 152074 Hom.: 12505 Cov.: 32 AF XY: 0.396 AC XY: 29391 AN XY: 74308

African (AFR) AF: 0.224 AC: 9299 AN: 41502

American (AMR) AF: 0.441 AC: 6742 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3470

East Asian (EAS) AF: 0.544 AC: 2817 AN: 5174

South Asian (SAS) AF: 0.516 AC: 2486 AN: 4822

European-Finnish (FIN) AF: 0.485 AC: 5109 AN: 10534

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.442 AC: 30030 AN: 67964

Other (OTH) AF: 0.437 AC: 923 AN: 2112

Alfa AF: 0.402 Hom.: 2212

Bravo AF: 0.384

Asia WGS AF: 0.479 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.20
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: rs3787348; hg19: chr20-49196998;