rs16989673

Variant names:

• chr20-50582818-C-CG
• rs16989673
• NM_002827.4:c.*104dupG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002827.4(PTPN1):​c.*104dupG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,430,574 control chromosomes in the GnomAD database, including 3,488 homozygotes. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.050 (270 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3218 hom.)
• Consequence: PTPN1 NM_002827.4 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -1.70
• Publications: 4 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.*104dupG		3_prime_UTR_variant	Exon 10 of 10	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.*104dupG		3_prime_UTR_variant	Exon 9 of 9		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.*104dupG		3_prime_UTR_variant	Exon 10 of 10	1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.*104dupG		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7621 AN: 152178 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.0671 AC: 85831 AN: 1278278 Hom.: 3218 Cov.: 18 AF XY: 0.0658 AC XY: 42034 AN XY: 639138

African (AFR) AF: 0.0122 AC: 363 AN: 29680

American (AMR) AF: 0.0302 AC: 1161 AN: 38400

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 1349 AN: 24198

East Asian (EAS) AF: 0.00 AC: 0 AN: 37354

South Asian (SAS) AF: 0.0201 AC: 1584 AN: 78618

European-Finnish (FIN) AF: 0.0690 AC: 3357 AN: 48648

Middle Eastern (MID) AF: 0.0539 AC: 253 AN: 4694

European-Non Finnish (NFE) AF: 0.0773 AC: 74449 AN: 962514

Other (OTH) AF: 0.0612 AC: 3315 AN: 54172

GnomAD4 genome AF: 0.0500 AC: 7621 AN: 152296 Hom.: 270 Cov.: 32 AF XY: 0.0498 AC XY: 3706 AN XY: 74474

African (AFR) AF: 0.0136 AC: 564 AN: 41566

American (AMR) AF: 0.0459 AC: 702 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4832

European-Finnish (FIN) AF: 0.0670 AC: 710 AN: 10600

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5161 AN: 68014

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0191 Hom.: 10

Bravo AF: 0.0468

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Insulin resistance, susceptibility to Other:1

Mar 01, 2002

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs16989673; hg19: chr20-49199355; COSMIC: COSV50405483; COSMIC: COSV50405483;