2-219290574-A-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_002846.4(PTPRN):c.2832T>G(p.His944Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

PTPRN
NM_002846.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.324

Publications

0 publications found

Variant links:

Genes affected

PTPRN (HGNC:9676): (protein tyrosine phosphatase receptor type N) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. 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 possesses an extracellular region, a single transmembrane region, and a single catalytic domain, and thus represents a receptor-type PTP. This PTP was found to be an autoantigen that is reactive with insulin-dependent diabetes mellitus (IDDM) patient sera, and thus may be a potential target of autoimmunity in diabetes mellitus. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Dec 2010]

PTPRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN	NM_002846.4 link	c.2832T>G	p.His944Gln	missense_variant	Exon 22 of 23	ENST00000295718.7	NP_002837.1	Q16849-1Q96IA0
PTPRN	NM_001199763.2 link	c.2745T>G	p.His915Gln	missense_variant	Exon 21 of 22		NP_001186692.1	Q16849-2
PTPRN	NM_001199764.2 link	c.2562T>G	p.His854Gln	missense_variant	Exon 22 of 23		NP_001186693.1	Q16849-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN	ENST00000295718.7 link	c.2832T>G	p.His944Gln	missense_variant	Exon 22 of 23	1	NM_002846.4	ENSP00000295718.2		Q16849-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000637

AC:

AN:

156934

AF XY:

0.0000121

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399512

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690274

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1079024

Other (OTH)

AF:

0.00

AC:

AN:

58020

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 20, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2832T>G (p.H944Q) alteration is located in exon 22 (coding exon 22) of the PTPRN gene. This alteration results from a T to G substitution at nucleotide position 2832, causing the histidine (H) at amino acid position 944 to be replaced by a glutamine (Q). 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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.74

.;D;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Uncertain

-0.090

MutationAssessor

Benign

0.56

.;N;.

PhyloP100

-0.32

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-7.7

D;D;.

REVEL

Uncertain

0.55

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.66

MutPred

0.47

.;Gain of disorder (P = 0.1737);.;

MVP

0.78

MPC

1.3

ClinPred

0.99

GERP RS

-1.8

Varity_R

0.89

gMVP

0.69

Mutation Taster

=35/64

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.44

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over