rs6020611

chr20-50578070-A-Gchr20-50578070-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN1	NM_002827.4	c.493-350A>G		intron_variant		ENST00000371621.5
PTPN1	NM_001278618.2	c.274-350A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN1	ENST00000371621.5	c.493-350A>G		intron_variant		1	NM_002827.4	P1
PTPN1	ENST00000541713.5	c.274-350A>G		intron_variant		2
	ENST00000431019.1			upstream_gene_variant		2

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

Gnomad4 AFR exome AF: 0.547

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.659

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.642

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

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.640

Alfa AF: 0.620 Hom.: 3648

Bravo AF: 0.619

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.0
Dann	Benign	0.49

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: rs6020611; hg19: chr20-49194607;