Genetic Variant PTPRS:p.Met1767Leu (chr19-5210741-T-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_002850.4(PTPRS):c.5299A>C(p.Met1767Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1767V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PTPRS
NM_002850.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.88

Publications

0 publications found

Variant links:

Genes affected

PTPRS (HGNC:9681): (protein tyrosine phosphatase receptor type S) 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 contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of multiple Ig-like and fibronectin type III-like domains. Studies of the similar gene in mice suggested that this PTP may be involved in cell-cell interaction, primary axonogenesis, and axon guidance during embryogenesis. This PTP has been also implicated in the molecular control of adult nerve repair. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRS links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32654113).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002850.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTPRS	NM_002850.4	MANE Select	c.5299A>C	p.Met1767Leu	missense	Exon 34 of 38	NP_002841.3
PTPRS	NM_001394011.1		c.5233A>C	p.Met1745Leu	missense	Exon 30 of 34	NP_001380940.1
PTPRS	NM_001394012.1		c.5212A>C	p.Met1738Leu	missense	Exon 30 of 34	NP_001380941.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRS	ENST00000262963.11	TSL:5 MANE Select	c.5299A>C	p.Met1767Leu	missense	Exon 34 of 38	ENSP00000262963.8	Q13332-1
PTPRS	ENST00000587303.5	TSL:1	c.5299A>C	p.Met1767Leu	missense	Exon 33 of 37	ENSP00000467537.1	Q13332-1
PTPRS	ENST00000588012.5	TSL:1	c.5185A>C	p.Met1729Leu	missense	Exon 28 of 32	ENSP00000465443.1	Q13332-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

251272

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.000176

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.021

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

4.9

PrimateAI

Uncertain

0.79

REVEL

Benign

0.16

Sift4G

Benign

0.14

Polyphen

0.0010

Vest4

0.50

MutPred

0.83

Loss of MoRF binding (P = 0.0798)

MVP

0.15

ClinPred

0.28

GERP RS

0.40

Varity_R

0.59

gMVP

0.90

Mutation Taster

=78/22

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over