12-15484006-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030667.3(PTPRO):c.108T>C(p.Asp36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,613,578 control chromosomes in the GnomAD database, including 896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (73 hom., cov: 32)
  • Exomes 𝑓: 0.030 (823 hom.)
• Consequence: PTPRO NM_030667.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00100

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-15484006-T-C is Benign according to our data. Variant chr12-15484006-T-C is described in ClinVar as [Benign]. Clinvar id is 1234355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.001 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0248 (3771/152268) while in subpopulation NFE AF= 0.036 (2449/67970). AF 95% confidence interval is 0.0348. There are 73 homozygotes in gnomad4. There are 1853 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 73 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRO	NM_030667.3	c.108T>C	p.Asp36=	synonymous_variant	2/27	ENST00000281171.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRO	ENST00000281171.9	c.108T>C	p.Asp36=	synonymous_variant	2/27	1	NM_030667.3	P4

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3772 AN: 152150 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.00586

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0237 AC: 5943 AN: 250984 Hom.: 103 AF XY: 0.0239 AC XY: 3237 AN XY: 135676

Gnomad AFR exome AF: 0.00474

Gnomad AMR exome AF: 0.0121

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00595

Gnomad FIN exome AF: 0.0524

Gnomad NFE exome AF: 0.0341

Gnomad OTH exome AF: 0.0273

GnomAD4 exome AF: 0.0297 AC: 43393 AN: 1461310 Hom.: 823 Cov.: 32 AF XY: 0.0291 AC XY: 21157 AN XY: 726976

Gnomad4 AFR exome AF: 0.00406

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00603

Gnomad4 FIN exome AF: 0.0516

Gnomad4 NFE exome AF: 0.0337

Gnomad4 OTH exome AF: 0.0266

GnomAD4 genome AF: 0.0248 AC: 3771 AN: 152268 Hom.: 73 Cov.: 32 AF XY: 0.0249 AC XY: 1853 AN XY: 74464

Gnomad4 AFR AF: 0.00584

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.0558

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0287 Hom.: 85

Bravo AF: 0.0199

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0316

EpiControl AF: 0.0290

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	4.6
Dann	Benign	0.63

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: rs17762440; hg19: chr12-15636940;