rs968701

Variant names:

• chr20-50578711-G-A
• rs968701
• NM_002827.4:c.702+82G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.95).
• 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 rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.702+82G>A		intron_variant	Intron 6 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.483+82G>A		intron_variant	Intron 5 of 8		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.702+82G>A		intron_variant	Intron 6 of 9	1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.483+82G>A		intron_variant	Intron 5 of 8	2		ENSP00000437732.1

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

African (AFR) AF: 0.291 AC: 6606 AN: 22734

American (AMR) AF: 0.520 AC: 12407 AN: 23864

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 9968 AN: 18876

East Asian (EAS) AF: 0.640 AC: 21912 AN: 34230

South Asian (SAS) AF: 0.629 AC: 39591 AN: 62964

European-Finnish (FIN) AF: 0.542 AC: 24361 AN: 44962

Middle Eastern (MID) AF: 0.587 AC: 1900 AN: 3236

European-Non Finnish (NFE) AF: 0.513 AC: 384176 AN: 749530

Other (OTH) AF: 0.519 AC: 22958 AN: 44220

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

African (AFR) AF: 0.299 AC: 12419 AN: 41478

American (AMR) AF: 0.499 AC: 7630 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3468

East Asian (EAS) AF: 0.624 AC: 3213 AN: 5150

South Asian (SAS) AF: 0.618 AC: 2980 AN: 4820

European-Finnish (FIN) AF: 0.536 AC: 5656 AN: 10548

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34867 AN: 67964

Other (OTH) AF: 0.499 AC: 1052 AN: 2110

Alfa AF: 0.495 Hom.: 23781

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
PhyloP100		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs968701; hg19: chr20-49195248;