rs968701

Positions:

• chr20-50578711-G-A
• chr20-50578711-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002827.4(PTPN1):​c.702+82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,156,644 control chromosomes in the GnomAD database, including 156,281 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 0.46 (17115 hom., cov: 32)
  • Exomes 𝑓: 0.52 (139166 hom.)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.702+82G>A		intron_variant		ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.483+82G>A		intron_variant			NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.702+82G>A		intron_variant		1	NM_002827.4	ENSP00000360683	P1
PTPN1	ENST00000541713.5	c.483+82G>A		intron_variant		2		ENSP00000437732

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70371 AN: 151912 Hom.: 17116 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.521 AC: 523879 AN: 1004616 Hom.: 139166 AF XY: 0.526 AC XY: 264708 AN XY: 503586

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.640

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.542

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.463 AC: 70387 AN: 152028 Hom.: 17115 Cov.: 32 AF XY: 0.466 AC XY: 34623 AN XY: 74300

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.499

Alfa AF: 0.503 Hom.: 18319

Bravo AF: 0.454

Asia WGS AF: 0.590 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.075
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs968701; hg19: chr20-49195248;