20-50526498-T-G

Variant names:

• chr20-50526498-T-G
• rs3787335
• NM_002827.4:c.63+15908T>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.63+15908T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,094 control chromosomes in the GnomAD database, including 1,240 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 0.12 (1240 hom., cov: 31)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 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.63+15908T>G		intron	N/A	NP_002818.1	A8K3M3
	PTPN1	NM_001278618.2		c.-66+15908T>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.63+15908T>G		intron	N/A	ENSP00000360683.3	P18031
	PTPN1	ENST00000859846.1		c.63+15908T>G		intron	N/A	ENSP00000529905.1
	PTPN1	ENST00000859845.1		c.63+15908T>G		intron	N/A	ENSP00000529904.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18659 AN: 151976 Hom.: 1240 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0995

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18673 AN: 152094 Hom.: 1240 Cov.: 31 AF XY: 0.125 AC XY: 9266 AN XY: 74366

African (AFR) AF: 0.160 AC: 6643 AN: 41470

American (AMR) AF: 0.0709 AC: 1084 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3470

East Asian (EAS) AF: 0.188 AC: 973 AN: 5176

South Asian (SAS) AF: 0.196 AC: 945 AN: 4816

European-Finnish (FIN) AF: 0.131 AC: 1390 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7115 AN: 67970

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.111 Hom.: 555

Bravo AF: 0.117

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.77
PhyloP100		-1.6
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: rs3787335; hg19: chr20-49143035;