rs6126033

Positions:

• chr20-50529572-C-T

Variant summary

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

The NM_002827.4(PTPN1):​c.63+18982C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 152,180 control chromosomes in the GnomAD database, including 634 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 0.088 (634 hom., cov: 32)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN1	NM_002827.4	c.63+18982C>T		intron_variant		ENST00000371621.5
PTPN1	NM_001278618.2	c.-66+18982C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN1	ENST00000371621.5	c.63+18982C>T		intron_variant		1	NM_002827.4	P1
PTPN1	ENST00000541713.5	c.-66+18982C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13324 AN: 152062 Hom.: 636 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.0724

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

GnomAD4 genome AF: 0.0876 AC: 13325 AN: 152180 Hom.: 634 Cov.: 32 AF XY: 0.0917 AC XY: 6822 AN XY: 74388

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.0712

Alfa AF: 0.0864 Hom.: 83

Bravo AF: 0.0779

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.52

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: rs6126033; hg19: chr20-49146109;