NM_002827.4:c.493-350A>G

Variant names:

• chr20-50578070-A-G
• rs6020611
• NM_002827.4:c.493-350A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002827.4(PTPN1):​c.493-350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 178,794 control chromosomes in the GnomAD database, including 34,759 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 0.62 (29201 hom., cov: 33)
  • Exomes 𝑓: 0.63 (5558 hom.)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• 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

ENSG00000232043 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

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.493-350A>G		intron	N/A	NP_002818.1	A8K3M3
	PTPN1	NM_001278618.2		c.274-350A>G		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.493-350A>G		intron	N/A	ENSP00000360683.3	P18031
	PTPN1	ENST00000859846.1		c.493-350A>G		intron	N/A	ENSP00000529905.1
	PTPN1	ENST00000859845.1		c.493-1098A>G		intron	N/A	ENSP00000529904.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94111 AN: 151504 Hom.: 29177 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.626 AC: 17001 AN: 27172 Hom.: 5558 Cov.: 0 AF XY: 0.627 AC XY: 9127 AN XY: 14548

African (AFR) AF: 0.547 AC: 394 AN: 720

American (AMR) AF: 0.581 AC: 1037 AN: 1784

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 494 AN: 762

East Asian (EAS) AF: 0.675 AC: 954 AN: 1414

South Asian (SAS) AF: 0.659 AC: 2064 AN: 3134

European-Finnish (FIN) AF: 0.602 AC: 643 AN: 1068

Middle Eastern (MID) AF: 0.718 AC: 79 AN: 110

European-Non Finnish (NFE) AF: 0.622 AC: 10446 AN: 16794

Other (OTH) AF: 0.642 AC: 890 AN: 1386

GnomAD4 genome AF: 0.621 AC: 94181 AN: 151622 Hom.: 29201 Cov.: 33 AF XY: 0.623 AC XY: 46139 AN XY: 74114

African (AFR) AF: 0.577 AC: 23821 AN: 41316

American (AMR) AF: 0.610 AC: 9312 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2255 AN: 3464

East Asian (EAS) AF: 0.675 AC: 3464 AN: 5132

South Asian (SAS) AF: 0.670 AC: 3224 AN: 4814

European-Finnish (FIN) AF: 0.635 AC: 6678 AN: 10516

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43208 AN: 67818

Other (OTH) AF: 0.640 AC: 1351 AN: 2110

Alfa AF: 0.620 Hom.: 3779

Bravo AF: 0.619

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		0.39
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: rs6020611; hg19: chr20-49194607;