Genetic Variant PTPRS:c.-94-1937T>G (chr19-5288171-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002850.4(PTPRS):c.-94-1937T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,140 control chromosomes in the GnomAD database, including 2,886 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 0.18 ( 2886 hom., cov: 32)

Consequence

PTPRS
NM_002850.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.841

Publications

4 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

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	Effect	Exon Rank	Protein
PTPRS	NM_002850.4	MANE Select	c.-94-1937T>G	intron	N/A	NP_002841.3
PTPRS	NM_001394011.1		c.-94-1937T>G	intron	N/A	NP_001380940.1
PTPRS	NM_001394012.1		c.-94-1937T>G	intron	N/A	NP_001380941.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTPRS	ENST00000262963.11	TSL:5 MANE Select	c.-94-1937T>G	intron	N/A	ENSP00000262963.8	Q13332-1
PTPRS	ENST00000588552.5	TSL:1	n.141-1937T>G	intron	N/A
PTPRS	ENST00000919618.1		c.-94-1937T>G	intron	N/A	ENSP00000589677.1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28090

AN:

152022

Hom.:

2888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.00597

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.173

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

GnomAD4 genome

AF:

0.185

AC:

28087

AN:

152140

Hom.:

2886

Cov.:

AF XY:

0.181

AC XY:

13431

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.138

AC:

5716

AN:

41514

American (AMR)

AF:

0.152

AC:

2327

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

581

AN:

3470

East Asian (EAS)

AF:

0.00579

AC:

AN:

5180

South Asian (SAS)

AF:

0.112

AC:

540

AN:

4816

European-Finnish (FIN)

AF:

0.223

AC:

2357

AN:

10584

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16052

AN:

67980

Other (OTH)

AF:

0.170

AC:

359

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1145

2290

3434

4579

5724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.211

Hom.:

11051

Bravo

AF:

0.180

Asia WGS

AF:

0.0770

AC:

269

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.43

(source)

DANN

Benign

0.44

PhyloP100

-0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over