20-50546698-A-G

Position:

• chr20-50546698-A-G

Variant summary

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

The NM_002827.4(PTPN1):​c.64-14665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,088 control chromosomes in the GnomAD database, including 12,998 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 0.40 (12998 hom., cov: 32)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.64-14665A>G		intron_variant		ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.-65-18271A>G		intron_variant			NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.64-14665A>G		intron_variant		1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.-65-18271A>G		intron_variant		2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61389 AN: 151970 Hom.: 12993 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.404 AC: 61414 AN: 152088 Hom.: 12998 Cov.: 32 AF XY: 0.406 AC XY: 30203 AN XY: 74326

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.446

Alfa AF: 0.443 Hom.: 31021

Bravo AF: 0.397

Asia WGS AF: 0.482 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.2
DANN	Benign	0.84

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: rs941798; hg19: chr20-49163235;