rs13041704

Variant names:

• chr20-50527746-A-C
• rs13041704
• NM_002827.4:c.63+17156A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-50527746-A-C
• chr20-50527746-A-G

Variant summary

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

The NM_002827.4(PTPN1):​c.63+17156A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,016 control chromosomes in the GnomAD database, including 10,229 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 0.37 (10229 hom., cov: 31)
• Consequence: PTPN1 NM_002827.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681
• Publications: 5 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 (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4	c.63+17156A>C		intron_variant	Intron 1 of 9	ENST00000371621.5	NP_002818.1
PTPN1	NM_001278618.2	c.-66+17156A>C		intron_variant	Intron 1 of 8		NP_001265547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5	c.63+17156A>C		intron_variant	Intron 1 of 9	1	NM_002827.4	ENSP00000360683.3
PTPN1	ENST00000541713.5	c.-66+17156A>C		intron_variant	Intron 1 of 8	2		ENSP00000437732.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55925 AN: 151898 Hom.: 10219 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.368 AC: 55964 AN: 152016 Hom.: 10229 Cov.: 31 AF XY: 0.366 AC XY: 27182 AN XY: 74318

African (AFR) AF: 0.374 AC: 15477 AN: 41426

American (AMR) AF: 0.391 AC: 5985 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5180

South Asian (SAS) AF: 0.330 AC: 1588 AN: 4816

European-Finnish (FIN) AF: 0.365 AC: 3860 AN: 10568

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25398 AN: 67960

Other (OTH) AF: 0.349 AC: 735 AN: 2106

Alfa AF: 0.367 Hom.: 26542

Bravo AF: 0.370

Asia WGS AF: 0.291 AC: 1011 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	4.2
DANN	Benign	0.67
PhyloP100		0.68
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: rs13041704; hg19: chr20-49144283;