20-50580062-C-T

Variant names:

• chr20-50580062-C-T
• rs718049
• NM_002827.4:c.1088+136C>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+136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 798,374 control chromosomes in the GnomAD database, including 149,843 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 0.57 (24923 hom., cov: 32)
  • Exomes 𝑓: 0.62 (124920 hom.)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 12 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 (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.1088+136C>T		intron_variant	Intron 8 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.869+136C>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+136C>T		intron_variant	Intron 8 of 9	1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.869+136C>T		intron_variant	Intron 7 of 8	2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86152 AN: 151706 Hom.: 24911 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.619 AC: 400358 AN: 646550 Hom.: 124920 AF XY: 0.622 AC XY: 208101 AN XY: 334406

African (AFR) AF: 0.441 AC: 7147 AN: 16222

American (AMR) AF: 0.579 AC: 14804 AN: 25586

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 9887 AN: 16004

East Asian (EAS) AF: 0.642 AC: 20710 AN: 32282

South Asian (SAS) AF: 0.668 AC: 35618 AN: 53322

European-Finnish (FIN) AF: 0.639 AC: 24287 AN: 38016

Middle Eastern (MID) AF: 0.690 AC: 1679 AN: 2434

European-Non Finnish (NFE) AF: 0.619 AC: 266260 AN: 430252

Other (OTH) AF: 0.616 AC: 19966 AN: 32432

GnomAD4 genome AF: 0.568 AC: 86201 AN: 151824 Hom.: 24923 Cov.: 32 AF XY: 0.570 AC XY: 42290 AN XY: 74178

African (AFR) AF: 0.438 AC: 18135 AN: 41424

American (AMR) AF: 0.579 AC: 8829 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2144 AN: 3468

East Asian (EAS) AF: 0.628 AC: 3227 AN: 5138

South Asian (SAS) AF: 0.655 AC: 3157 AN: 4820

European-Finnish (FIN) AF: 0.630 AC: 6632 AN: 10520

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.618 AC: 41930 AN: 67890

Other (OTH) AF: 0.608 AC: 1282 AN: 2110

Alfa AF: 0.589 Hom.: 5451

Bravo AF: 0.560

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	-0.87
CADD	Benign	1.0
DANN	Benign	0.61
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs718049; hg19: chr20-49196599;