12-15483987-T-C

Variant names:

• chr12-15483987-T-C
• NM_030667.3:c.89T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030667.3(PTPRO):​c.89T>C​(p.Phe30Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PTPRO NM_030667.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 6

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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, 0.815

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030667.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	NM_030667.3	MANE Select	c.89T>C	p.Phe30Ser	missense	Exon 2 of 27	NP_109592.1	Q16827-1
	PTPRO	NM_002848.4		c.89T>C	p.Phe30Ser	missense	Exon 2 of 26	NP_002839.1	Q16827-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	ENST00000281171.9	TSL:1 MANE Select	c.89T>C	p.Phe30Ser	missense	Exon 2 of 27	ENSP00000281171.4	Q16827-1
	PTPRO	ENST00000348962.7	TSL:1	c.89T>C	p.Phe30Ser	missense	Exon 2 of 26	ENSP00000343434.2	Q16827-2
	PTPRO	ENST00000543886.6	TSL:1	c.89T>C	p.Phe30Ser	missense	Exon 2 of 9	ENSP00000444173.1	Q16827-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.82	P
Vest4		0.88
MutPred		0.63		Gain of catalytic residue at K25 (P = 0.0046)
MVP		0.54
MPC		1.1
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.51
gMVP		0.84
Mutation Taster		=35/65	disease causing

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

Other links and lift over

hg19: chr12-15636921;