rs2230601

chr18-8069870-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001105244.2(PTPRM):c.1317C>T(p.Asn439=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,612,754 control chromosomes in the GnomAD database, including 226,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21004 hom., cov: 31)
  • Exomes 𝑓: 0.53 (205554 hom.)
• Consequence: PTPRM NM_001105244.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0700

Genes affected

PTPRM (HGNC:9675): (protein tyrosine phosphatase receptor type M) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP has been shown to mediate cell-cell aggregation through the interaction with another molecule of this PTP on an adjacent cell. This PTP can interact with scaffolding protein RACK1/GNB2L1, which may be necessary for the downstream signaling in response to cell-cell adhesion. Alternative splicing results in multiple transcripts encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 18-8069870-C-T is Benign according to our data. Variant chr18-8069870-C-T is described in ClinVar as [Benign]. Clinvar id is 3060529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRM	NM_001105244.2	c.1317C>T	p.Asn439=	synonymous_variant	8/33	ENST00000580170.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRM	ENST00000580170.6	c.1317C>T	p.Asn439=	synonymous_variant	8/33	1	NM_001105244.2	A1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79617 AN: 151804 Hom.: 20967 Cov.: 31

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.517

GnomAD3 exomes AF: 0.498 AC: 124505 AN: 250200 Hom.: 31712 AF XY: 0.498 AC XY: 67314 AN XY: 135192

Gnomad AFR exome AF: 0.561

Gnomad AMR exome AF: 0.474

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.271

Gnomad SAS exome AF: 0.494

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.533

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.527 AC: 769998 AN: 1460832 Hom.: 205554 Cov.: 56 AF XY: 0.526 AC XY: 382104 AN XY: 726658

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.479

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.525 AC: 79708 AN: 151922 Hom.: 21004 Cov.: 31 AF XY: 0.523 AC XY: 38858 AN XY: 74250

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.515

Alfa AF: 0.521 Hom.: 50020

Bravo AF: 0.524

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PTPRM-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	2.3
Dann	Benign	0.64

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: rs2230601; hg19: chr18-8069868; COSMIC: COSV59844912; COSMIC: COSV59844912;