20-50526498-T-G

Position:

• chr20-50526498-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.63+15908T>G		intron_variant		ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.-66+15908T>G		intron_variant			NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.63+15908T>G		intron_variant		1	NM_002827.4	ENSP00000360683	P1
PTPN1	ENST00000541713.5	c.-66+15908T>G		intron_variant		2		ENSP00000437732

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

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0709

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.112 Hom.: 507

Bravo AF: 0.117

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.77

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: rs3787335; hg19: chr20-49143035;