chr12-15484466-T-G

Position:

• chr12-15484466-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030667.3(PTPRO):​c.349+219T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,060 control chromosomes in the GnomAD database, including 2,677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2677 hom., cov: 32)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.969

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-15484466-T-G is Benign according to our data. Variant chr12-15484466-T-G is described in ClinVar as [Benign]. Clinvar id is 1262483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRO	NM_030667.3	c.349+219T>G		intron_variant		ENST00000281171.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRO	ENST00000281171.9	c.349+219T>G		intron_variant		1	NM_030667.3	P4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26755 AN: 151942 Hom.: 2679 Cov.: 32

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26755 AN: 152060 Hom.: 2677 Cov.: 32 AF XY: 0.180 AC XY: 13384 AN XY: 74324

Gnomad4 AFR AF: 0.0837

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.189

Alfa AF: 0.207 Hom.: 4004

Bravo AF: 0.169

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.77

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

LitVar

Other links and lift over

dbSNP: rs11056519; hg19: chr12-15637400;