dbSNP rs1952194120: PTPRN:p.Val805Ala (chr2-219296320-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002846.4(PTPRN):c.2414T>C(p.Val805Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V805D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PTPRN
NM_002846.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.29

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN	NM_002846.4 link	c.2414T>C	p.Val805Ala	missense_variant	Exon 18 of 23	ENST00000295718.7	NP_002837.1	Q16849-1Q96IA0
PTPRN	NM_001199763.2 link	c.2327T>C	p.Val776Ala	missense_variant	Exon 17 of 22		NP_001186692.1	Q16849-2
PTPRN	NM_001199764.2 link	c.2144T>C	p.Val715Ala	missense_variant	Exon 18 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.2414T>C	p.Val805Ala	missense_variant	Exon 18 of 23	1	NM_002846.4	ENSP00000295718.2		Q16849-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

.;D;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.068

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

1.8

.;L;.

PhyloP100

9.3

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-4.0

D;D;.

REVEL

Pathogenic

0.91

Sift

Uncertain

0.010

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.73

.;P;.

Vest4

0.87

MutPred

0.68

.;Gain of glycosylation at S801 (P = 0.1497);.;

MVP

0.88

MPC

1.4

ClinPred

0.99

GERP RS

4.7

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.78

gMVP

0.57

Mutation Taster

=17/83

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over