rs1130496

Variant names:

• chr7-158167203-C-T
• rs1130496
• NM_002847.5:c.638G>A

Variant summary

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

The NM_002847.5(PTPRN2):​c.638G>A​(p.Arg213His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,612,628 control chromosomes in the GnomAD database, including 135,075 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.35 (10490 hom., cov: 32)
  • Exomes 𝑓: 0.41 (124585 hom.)
• Consequence: PTPRN2 NM_002847.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

Genes affected

PTPRN2 (HGNC:9677): (protein tyrosine phosphatase receptor type N2) This gene encodes a protein with sequence similarity to receptor-like protein tyrosine phosphatases. However, tyrosine phosphatase activity has not been experimentally validated for this protein. Studies of the rat ortholog suggest that the encoded protein may instead function as a phosphatidylinositol phosphatase with the ability to dephosphorylate phosphatidylinositol 3-phosphate and phosphatidylinositol 4,5-diphosphate, and this function may be involved in the regulation of insulin secretion. This protein has been identified as an autoantigen in insulin-dependent diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011554658).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN2	NM_002847.5	c.638G>A	p.Arg213His	missense_variant	Exon 6 of 23	ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9	c.638G>A	p.Arg213His	missense_variant	Exon 6 of 23	1	NM_002847.5	ENSP00000374069.4
PTPRN2	ENST00000389416.8	c.587G>A	p.Arg196His	missense_variant	Exon 5 of 22	1		ENSP00000374067.4
PTPRN2	ENST00000389413.7	c.638G>A	p.Arg213His	missense_variant	Exon 6 of 22	1		ENSP00000374064.3
PTPRN2	ENST00000409483.5	c.524G>A	p.Arg175His	missense_variant	Exon 5 of 22	2		ENSP00000387114.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53570 AN: 151678 Hom.: 10478 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.398

GnomAD3 exomes AF: 0.404 AC: 100071 AN: 247926 Hom.: 20912 AF XY: 0.402 AC XY: 54047 AN XY: 134390

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.434

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.385

Gnomad NFE exome AF: 0.429

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.410 AC: 599044 AN: 1460834 Hom.: 124585 Cov.: 65 AF XY: 0.409 AC XY: 297004 AN XY: 726738

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.452

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.372

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.353 AC: 53591 AN: 151794 Hom.: 10490 Cov.: 32 AF XY: 0.354 AC XY: 26254 AN XY: 74172

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.399

Alfa AF: 0.411 Hom.: 8330

Bravo AF: 0.349

TwinsUK AF: 0.419 AC: 1555

ALSPAC AF: 0.410 AC: 1581

ESP6500AA AF: 0.169 AC: 746

ESP6500EA AF: 0.434 AC: 3733

ExAC AF: 0.395 AC: 47989

Asia WGS AF: 0.362 AC: 1263 AN: 3478

EpiCase AF: 0.422

EpiControl AF: 0.427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.015	.;.;.;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.56	T;T;T;T;T
MetaRNN	Benign	0.0012	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.;N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.030	N;N;N;N;.
REVEL	Benign	0.21
Sift	Uncertain	0.012	D;T;T;T;.
Sift4G	Benign	0.57	T;T;T;T;T
Polyphen		0.82	P;P;.;P;.
Vest4		0.13
MPC		0.25
ClinPred		0.010	T
GERP RS		3.7
Varity_R		0.029
gMVP		0.35

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: rs1130496; hg19: chr7-157959895; COSMIC: COSV67046421;