Genetic Variant NM_001105244.2:c.3055-5926G>T (chr18-8364964-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001105244.2(PTPRM):c.3055-5926G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,982 control chromosomes in the GnomAD database, including 14,979 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 0.44 ( 14964 hom., cov: 32)

Exomes 𝑓: 0.62 ( 15 hom. )

Consequence

PTPRM
NM_001105244.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.109

Publications

4 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:

ENSG00000266149 (HGNC:):

ENSG00000266149 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.3055-5926G>T		intron_variant	Intron 23 of 32	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.3055-5926G>T		intron_variant	Intron 23 of 32	1	NM_001105244.2	ENSP00000463325.1		P28827-2

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66062

AN:

151796

Hom.:

14944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.562

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.438

GnomAD4 exome

AF:

0.618

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.795

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.654

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.435

AC:

66132

AN:

151914

Hom.:

14964

Cov.:

AF XY:

0.432

AC XY:

32110

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.562

AC:

23266

AN:

41408

American (AMR)

AF:

0.342

AC:

5230

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1132

AN:

3468

East Asian (EAS)

AF:

0.308

AC:

1592

AN:

5164

South Asian (SAS)

AF:

0.462

AC:

2222

AN:

4810

European-Finnish (FIN)

AF:

0.425

AC:

4483

AN:

10548

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.395

AC:

26850

AN:

67934

Other (OTH)

AF:

0.438

AC:

923

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1861

3721

5582

7442

9303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.410

Hom.:

2623

Bravo

AF:

0.430

Asia WGS

AF:

0.410

AC:

1427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

(source)

DANN

Benign

0.52

PhyloP100

0.11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over