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GeneBe

12-15322748-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030667.3(PTPRO):c.22A>C(p.Ile8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I8T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PTPRO
NM_030667.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.130
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.062089533).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTPRONM_030667.3 linkuse as main transcriptc.22A>C p.Ile8Leu missense_variant 1/27 ENST00000281171.9
LOC105369673XR_007063224.1 linkuse as main transcriptn.332+14629T>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTPROENST00000281171.9 linkuse as main transcriptc.22A>C p.Ile8Leu missense_variant 1/271 NM_030667.3 P4Q16827-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsAug 16, 2022The c.22A>C (p.I8L) alteration is located in exon 1 (coding exon 1) of the PTPRO gene. This alteration results from a A to C substitution at nucleotide position 22, causing the isoleucine (I) at amino acid position 8 to be replaced by a leucine (L). 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
0.075
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
Cadd
Benign
2.4
Dann
Benign
0.67
DEOGEN2
Benign
0.094
T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.044
N
LIST_S2
Benign
0.59
T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.062
T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.55
N;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.020
N;N;N
REVEL
Benign
0.017
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.27
T;T;T
Polyphen
0.0
B;.;B
Vest4
0.096
MutPred
0.24
Gain of catalytic residue at T6 (P = 0);Gain of catalytic residue at T6 (P = 0);Gain of catalytic residue at T6 (P = 0);
MVP
0.17
MPC
0.27
ClinPred
0.027
T
GERP RS
1.7
Varity_R
0.069
gMVP
0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-15475682; API