7-158587563-C-T

Position:

chr7-158587563-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000389418.9(PTPRN2):c.107G>A(p.Arg36His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,329,572 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000074 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00021 ( 4 hom. )

Consequence

PTPRN2
ENST00000389418.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0210

Variant links:

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]

PTPRN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034997076).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRN2	NM_002847.5 linkuse as main transcript	c.107G>A	p.Arg36His	missense_variant	1/23	ENST00000389418.9	NP_002838.2	Q92932-1I6L9F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTPRN2	ENST00000389418.9 linkuse as main transcript	c.107G>A	p.Arg36His	missense_variant	1/23	1	NM_002847.5	ENSP00000374069.4	Q92932-1
PTPRN2	ENST00000389416.8 linkuse as main transcript	c.107G>A	p.Arg36His	missense_variant	1/22	1		ENSP00000374067.4	Q92932-4
PTPRN2	ENST00000389413.7 linkuse as main transcript	c.107G>A	p.Arg36His	missense_variant	1/22	1		ENSP00000374064.3	Q92932-2
PTPRN2	ENST00000409483.5 linkuse as main transcript	c.107G>A	p.Arg36His	missense_variant	1/22	2		ENSP00000387114.1	E7EM83

Frequencies

GnomAD3 genomes

AF:

0.0000738

AC:

AN:

149110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00121

Gnomad SAS

AF:

0.000214

Gnomad FIN

AF:

0.000197

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.000490

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

20362

Hom.:

AF XY:

0.00

AC XY:

AN XY:

11468

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000826

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000213

AC:

251

AN:

1180350

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

119

AN XY:

570788

show subpopulations

Gnomad4 AFR exome

AF:

0.0000422

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00729

Gnomad4 SAS exome

AF:

0.000349

Gnomad4 FIN exome

AF:

0.000326

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000147

GnomAD4 genome

AF:

0.0000737

AC:

AN:

149222

Hom.:

Cov.:

AF XY:

0.0000687

AC XY:

AN XY:

72806

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00122

Gnomad4 SAS

AF:

0.000214

Gnomad4 FIN

AF:

0.000197

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000836

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.107G>A (p.R36H) alteration is located in exon 1 (coding exon 1) of the PTPRN2 gene. This alteration results from a G to A substitution at nucleotide position 107, causing the arginine (R) at amino acid position 36 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

.;.;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.65

T;T;T;T

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.035

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.69

N;.;N;N

MutationTaster

Benign

0.86

N;N;N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.58

N;N;N;N

REVEL

Benign

0.070

Sift

Uncertain

0.010

D;D;T;D

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.98

D;D;.;D

Vest4

0.12

MVP

0.31

MPC

0.75

ClinPred

0.27

GERP RS

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.067

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over