rs2230601

Variant names:

• chr18-8069870-C-T
• rs2230601
• NM_001105244.2:c.1317C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001105244.2(PTPRM):​c.1317C>T​(p.Asn439Asn) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.52 (21004 hom., cov: 31)
  • Exomes 𝑓: 0.53 (205554 hom.)
• Consequence: PTPRM NM_001105244.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0700
• Publications: 21 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 -14 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 VariationId is 3060529.Status of the report is no_assertion_criteria_provided, 0 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	NM_001105244.2	MANE Select	c.1317C>T	p.Asn439Asn	synonymous	Exon 8 of 33	NP_001098714.1	P28827-2
	PTPRM	NM_002845.4		c.1317C>T	p.Asn439Asn	synonymous	Exon 8 of 31	NP_002836.3
	PTPRM	NM_001378147.1		c.678C>T	p.Asn226Asn	synonymous	Exon 4 of 31	NP_001365076.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRM	ENST00000580170.6	TSL:1 MANE Select	c.1317C>T	p.Asn439Asn	synonymous	Exon 8 of 33	ENSP00000463325.1	P28827-2
	PTPRM	ENST00000332175.12	TSL:1	c.1317C>T	p.Asn439Asn	synonymous	Exon 8 of 31	ENSP00000331418.8	P28827-1
	PTPRM	ENST00000400053.8	TSL:5	c.1131C>T	p.Asn377Asn	synonymous	Exon 8 of 31	ENSP00000382927.4	E7EPS8

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

GnomAD2 exomes AF: 0.498 AC: 124505 AN: 250200 AF XY: 0.498

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 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

African (AFR) AF: 0.557 AC: 18658 AN: 33470

American (AMR) AF: 0.479 AC: 21367 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11505 AN: 26132

East Asian (EAS) AF: 0.266 AC: 10559 AN: 39680

South Asian (SAS) AF: 0.498 AC: 42950 AN: 86204

European-Finnish (FIN) AF: 0.534 AC: 28522 AN: 53390

Middle Eastern (MID) AF: 0.451 AC: 2600 AN: 5766

European-Non Finnish (NFE) AF: 0.542 AC: 602846 AN: 1111246

Other (OTH) AF: 0.513 AC: 30991 AN: 60368

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

African (AFR) AF: 0.562 AC: 23278 AN: 41438

American (AMR) AF: 0.507 AC: 7747 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3464

East Asian (EAS) AF: 0.267 AC: 1370 AN: 5140

South Asian (SAS) AF: 0.492 AC: 2365 AN: 4806

European-Finnish (FIN) AF: 0.515 AC: 5436 AN: 10548

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36271 AN: 67938

Other (OTH) AF: 0.515 AC: 1087 AN: 2110

Alfa AF: 0.523 Hom.: 74470

Bravo AF: 0.524

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PTPRM-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		-0.070
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: rs2230601; hg19: chr18-8069868; COSMIC: COSV59844912; COSMIC: COSV59844912;