rs3215684

Positions:

• chr20-50578329-A-AT
• chr20-50578329-A-ATC

Variant summary

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

The NM_002827.4(PTPN1):​c.493-91_493-90insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,080,034 control chromosomes in the GnomAD database, including 222,650 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (29647 hom., cov: 0)
  • Exomes 𝑓: 0.64 (193003 hom.)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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 (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.493-91_493-90insT		intron_variant		ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.274-91_274-90insT		intron_variant			NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.493-91_493-90insT		intron_variant		1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.274-91_274-90insT		intron_variant		2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94922 AN: 151842 Hom.: 29624 Cov.: 0

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.643 AC: 596431 AN: 928074 Hom.: 193003 AF XY: 0.644 AC XY: 307073 AN XY: 476748

Gnomad4 AFR exome AF: 0.589

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.625 AC: 94990 AN: 151960 Hom.: 29647 Cov.: 0 AF XY: 0.626 AC XY: 46507 AN XY: 74264

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.639

Alfa AF: 0.623 Hom.: 3611

Bravo AF: 0.623

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3215684; hg19: chr20-49194866; COSMIC: COSV65407183; COSMIC: COSV65407183;