rs6506569

Variant names:

• chr18-8275859-T-C
• rs6506569
• NM_001105244.2:c.2755-20509T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105244.2(PTPRM):​c.2755-20509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,878 control chromosomes in the GnomAD database, including 18,572 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 0.49 (18572 hom., cov: 32)
• Consequence: PTPRM NM_001105244.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105244.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	NM_001105244.2	MANE Select	c.2755-20509T>C		intron	N/A	NP_001098714.1
	PTPRM	NM_002845.4		c.2716-20509T>C		intron	N/A	NP_002836.3
	PTPRM	NM_001378147.1		c.2191-20509T>C		intron	N/A	NP_001365076.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	ENST00000580170.6	TSL:1 MANE Select	c.2755-20509T>C		intron	N/A	ENSP00000463325.1
	PTPRM	ENST00000332175.12	TSL:1	c.2716-20509T>C		intron	N/A	ENSP00000331418.8
	PTPRM	ENST00000400053.8	TSL:5	c.2530-20509T>C		intron	N/A	ENSP00000382927.4

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74768 AN: 151760 Hom.: 18554 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.493 AC: 74829 AN: 151878 Hom.: 18572 Cov.: 32 AF XY: 0.497 AC XY: 36870 AN XY: 74236

African (AFR) AF: 0.511 AC: 21157 AN: 41418

American (AMR) AF: 0.558 AC: 8516 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1400 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2453 AN: 5146

South Asian (SAS) AF: 0.513 AC: 2459 AN: 4796

European-Finnish (FIN) AF: 0.496 AC: 5230 AN: 10550

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.472 AC: 32093 AN: 67922

Other (OTH) AF: 0.496 AC: 1045 AN: 2106

Alfa AF: 0.479 Hom.: 77385

Bravo AF: 0.499

Asia WGS AF: 0.520 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.81
DANN	Benign	0.41
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs6506569; hg19: chr18-8275857;