Genetic Variant NM_001105244.2:c.1317C>T (chr18-8069870-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0700

Publications

21 publications found

Variant links:

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]

PTPRM links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRM	NM_001105244.2 link	c.1317C>T	p.Asn439Asn	synonymous_variant	Exon 8 of 33	ENST00000580170.6	NP_001098714.1	P28827-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRM	ENST00000580170.6 link	c.1317C>T	p.Asn439Asn	synonymous_variant	Exon 8 of 33	1	NM_001105244.2	ENSP00000463325.1		P28827-2

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79617

AN:

151804

Hom.:

20967

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.526

AC XY:

382104

AN XY:

726658

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

20568

41135

61703

82270

102838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17004

34008

51012

68016

85020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.525

AC:

79708

AN:

151922

Hom.:

21004

Cov.:

AF XY:

0.523

AC XY:

38858

AN XY:

74250

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1935

3870

5804

7739

9674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.523

Hom.:

74470

Bravo

AF:

0.524

Asia WGS

AF:

0.393

AC:

1366

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTPRM-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.64

PhyloP100

-0.070

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over