rs253810

chr12-15463610-A-Gchr12-15463610-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030667.3(PTPRO):c.76-20364A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,166 control chromosomes in the GnomAD database, including 65,213 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (65213 hom., cov: 31)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRO	NM_030667.3	c.76-20364A>G		intron_variant		ENST00000281171.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRO	ENST00000281171.9	c.76-20364A>G		intron_variant		1	NM_030667.3	P4

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139925 AN: 152048 Hom.: 65177 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.920 AC: 140019 AN: 152166 Hom.: 65213 Cov.: 31 AF XY: 0.922 AC XY: 68591 AN XY: 74388

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.977

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.992

Gnomad4 OTH AF: 0.931

Alfa AF: 0.954 Hom.: 10174

Bravo AF: 0.910

Asia WGS AF: 0.906 AC: 3148 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.3
Dann	Benign	0.59

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: rs253810; hg19: chr12-15616544;