chr20-50579630-T-C

Variant names:

• chr20-50579630-T-C
• rs2282147
• NM_002827.4:c.865-73T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002827.4(PTPN1):​c.865-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,337,584 control chromosomes in the GnomAD database, including 276,401 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 (29247 hom., cov: 32)
  • Exomes 𝑓: 0.64 (247154 hom.)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.865-73T>C		intron_variant	Intron 7 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.646-73T>C		intron_variant	Intron 6 of 8		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.865-73T>C		intron_variant	Intron 7 of 9	1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.646-73T>C		intron_variant	Intron 6 of 8	2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94198 AN: 151926 Hom.: 29220 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.645 AC: 764082 AN: 1185540 Hom.: 247154 AF XY: 0.645 AC XY: 385808 AN XY: 597764

African (AFR) AF: 0.576 AC: 15919 AN: 27656

American (AMR) AF: 0.588 AC: 24616 AN: 41850

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 14681 AN: 22662

East Asian (EAS) AF: 0.696 AC: 26532 AN: 38140

South Asian (SAS) AF: 0.675 AC: 52353 AN: 77512

European-Finnish (FIN) AF: 0.648 AC: 33818 AN: 52210

Middle Eastern (MID) AF: 0.708 AC: 2533 AN: 3578

European-Non Finnish (NFE) AF: 0.644 AC: 560724 AN: 871232

Other (OTH) AF: 0.649 AC: 32906 AN: 50700

GnomAD4 genome AF: 0.620 AC: 94271 AN: 152044 Hom.: 29247 Cov.: 32 AF XY: 0.621 AC XY: 46178 AN XY: 74310

African (AFR) AF: 0.573 AC: 23762 AN: 41474

American (AMR) AF: 0.607 AC: 9274 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2262 AN: 3470

East Asian (EAS) AF: 0.680 AC: 3518 AN: 5172

South Asian (SAS) AF: 0.670 AC: 3229 AN: 4822

European-Finnish (FIN) AF: 0.640 AC: 6756 AN: 10550

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43234 AN: 67964

Other (OTH) AF: 0.645 AC: 1360 AN: 2110

Alfa AF: 0.629 Hom.: 13101

Bravo AF: 0.616

Asia WGS AF: 0.666 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.40
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: rs2282147; hg19: chr20-49196167;