Variant 7-158587575-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000389418.9(PTPRN2):c.95A>G(p.Gln32Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,328,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 25)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

PTPRN2
ENST00000389418.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00100

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0758594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRN2	NM_002847.5 linkuse as main transcript	c.95A>G	p.Gln32Arg	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.95A>G	p.Gln32Arg	missense_variant	1/23	1	NM_002847.5	ENSP00000374069.4	Q92932-1
PTPRN2	ENST00000389416.8 linkuse as main transcript	c.95A>G	p.Gln32Arg	missense_variant	1/22	1		ENSP00000374067.4	Q92932-4
PTPRN2	ENST00000389413.7 linkuse as main transcript	c.95A>G	p.Gln32Arg	missense_variant	1/22	1		ENSP00000374064.3	Q92932-2
PTPRN2	ENST00000409483.5 linkuse as main transcript	c.95A>G	p.Gln32Arg	missense_variant	1/22	2		ENSP00000387114.1	E7EM83

Frequencies

GnomAD3 genomes

AF:

0.0000273

AC:

AN:

146278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.46e-7

AC:

AN:

1182088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

572380

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000273

AC:

AN:

146278

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71470

show subpopulations

Gnomad4 AFR

AF:

0.000101

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Aug 03, 2022

The c.95A>G (p.Q32R) alteration is located in exon 1 (coding exon 1) of the PTPRN2 gene. This alteration results from a A to G substitution at nucleotide position 95, causing the glutamine (Q) at amino acid position 32 to be replaced by an arginine (R). 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

Benign

0.097

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.032

.;.;.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.45

T;T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.32

T;D;T;T

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.0030

B;B;.;B

Vest4

0.16

MutPred

0.21

Gain of MoRF binding (P = 0.0622);Gain of MoRF binding (P = 0.0622);Gain of MoRF binding (P = 0.0622);Gain of MoRF binding (P = 0.0622);

MVP

0.20

MPC

0.40

ClinPred

0.14

GERP RS

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.083

gMVP

0.40

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