chr20-50578329-A-AC

Variant names:

• chr20-50578329-A-AC
• rs3215684
• NM_002827.4:c.493-91_493-90insC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002827.4(PTPN1):​c.493-91_493-90insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 930,082 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002827.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	NM_002827.4	MANE Select	c.493-91_493-90insC		intron	N/A	NP_002818.1	A8K3M3
	PTPN1	NM_001278618.2		c.274-91_274-90insC		intron	N/A	NP_001265547.1	B4DSN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN1	ENST00000371621.5	TSL:1 MANE Select	c.493-91_493-90insC		intron	N/A	ENSP00000360683.3	P18031
	PTPN1	ENST00000859846.1		c.493-91_493-90insC		intron	N/A	ENSP00000529905.1
	PTPN1	ENST00000859845.1		c.493-839_493-838insC		intron	N/A	ENSP00000529904.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000215 AC: 2 AN: 930082 Hom.: 0 AF XY: 0.00000209 AC XY: 1 AN XY: 477730

African (AFR) AF: 0.00 AC: 0 AN: 22634

American (AMR) AF: 0.00 AC: 0 AN: 39722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19830

East Asian (EAS) AF: 0.00 AC: 0 AN: 37122

South Asian (SAS) AF: 0.0000148 AC: 1 AN: 67488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4612

European-Non Finnish (NFE) AF: 0.00000153 AC: 1 AN: 652018

Other (OTH) AF: 0.00 AC: 0 AN: 42528

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.058

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: rs3215684; hg19: chr20-49194866;