rs16989673

chr20-50582818-C-CG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002827.4(PTPN1):c.*104dup 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PTPN1	NM_002827.4	c.*104dup		3_prime_UTR_variant	10/10	ENST00000371621.5
PTPN1	NM_001278618.2	c.*104dup		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN1	ENST00000371621.5	c.*104dup		3_prime_UTR_variant	10/10	1	NM_002827.4	P1
PTPN1	ENST00000541713.5	c.*104dup		3_prime_UTR_variant	9/9	2

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

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0302

Gnomad4 ASJ exome AF: 0.0557

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0201

Gnomad4 FIN exome AF: 0.0690

Gnomad4 NFE exome AF: 0.0773

Gnomad4 OTH exome AF: 0.0612

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

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.0507

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

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs16989673; hg19: chr20-49199355;