Genetic Variant NM_030667.3:c.65T>C (chr12-15322791-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030667.3(PTPRO):c.65T>C(p.Val22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PTPRO
NM_030667.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.482

Publications

0 publications found

Variant links:

Genes affected

PTPRO (HGNC:9678): (protein tyrosine phosphatase receptor type O) This gene encodes a member of the R3 subtype family of receptor-type protein tyrosine phosphatases. These proteins are localized to the apical surface of polarized cells and may have tissue-specific functions through activation of Src family kinases. This gene contains two distinct promoters, and alternatively spliced transcript variants encoding multiple isoforms have been observed. The encoded proteins may have multiple isoform-specific and tissue-specific functions, including the regulation of osteoclast production and activity, inhibition of cell proliferation and facilitation of apoptosis. This gene is a candidate tumor suppressor, and decreased expression of this gene has been observed in several types of cancer. [provided by RefSeq, May 2011]

PTPRO links:

LOC105369673 (HGNC:):

LOC105369673 links:

RERG (HGNC:15980): (RAS like estrogen regulated growth inhibitor) RERG, a member of the RAS superfamily of GTPases, inhibits cell proliferation and tumor formation (Finlin et al., 2001 [PubMed 11533059]).[supplied by OMIM, Mar 2009]

RERG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14805841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRO	NM_030667.3 link	c.65T>C	p.Val22Ala	missense_variant	Exon 1 of 27	ENST00000281171.9	NP_109592.1	Q16827-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRO	ENST00000281171.9 link	c.65T>C	p.Val22Ala	missense_variant	Exon 1 of 27	1	NM_030667.3	ENSP00000281171.4		Q16827-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5266

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111504

Other (OTH)

AF:

0.00

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 6

Uncertain:1

Feb 20, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

N;N;N

PhyloP100

0.48

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.58

N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0080

D;T;D

Polyphen

0.81

P;.;P

Vest4

0.10

MutPred

0.27

Gain of catalytic residue at L17 (P = 0);Gain of catalytic residue at L17 (P = 0);Gain of catalytic residue at L17 (P = 0);

MVP

0.32

MPC

0.35

ClinPred

0.78

GERP RS

3.9

PromoterAI

-0.056

Neutral

(source)

Varity_R

0.18

gMVP

0.25

Mutation Taster

=72/28

polymorphism

(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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NM_030667.3:c.65T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over