Genetic Variant NM_002850.4:c.261A>C (chr19-5273560-T-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002850.4(PTPRS):c.261A>C(p.Ala87Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,613,918 control chromosomes in the GnomAD database, including 37,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3953 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33916 hom. )

Consequence

PTPRS
NM_002850.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.08

Publications

13 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-5273560-T-G is Benign according to our data. Variant chr19-5273560-T-G is described in ClinVar as Benign. ClinVar VariationId is 1263463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRS	NM_002850.4 link	c.261A>C	p.Ala87Ala	synonymous_variant	Exon 4 of 38	ENST00000262963.11	NP_002841.3	Q13332-1Q8NHS7Q59FX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRS	ENST00000262963.11 link	c.261A>C	p.Ala87Ala	synonymous_variant	Exon 4 of 38	5	NM_002850.4	ENSP00000262963.8		Q13332-1G8JL96

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32804

AN:

151990

Hom.:

3947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.243

GnomAD2 exomes

AF:

0.182

AC:

45793

AN:

251308

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.000816

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.208

AC:

303685

AN:

1461810

Hom.:

33916

Cov.:

AF XY:

0.207

AC XY:

150180

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.264

AC:

8823

AN:

33476

American (AMR)

AF:

0.128

AC:

5708

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

8440

AN:

26132

East Asian (EAS)

AF:

0.000705

AC:

AN:

39700

South Asian (SAS)

AF:

0.130

AC:

11239

AN:

86254

European-Finnish (FIN)

AF:

0.153

AC:

8153

AN:

53420

Middle Eastern (MID)

AF:

0.280

AC:

1616

AN:

5768

European-Non Finnish (NFE)

AF:

0.222

AC:

246911

AN:

1111948

Other (OTH)

AF:

0.211

AC:

12767

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

13458

26916

40374

53832

67290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8306

16612

24918

33224

41530

<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:

0.216

AC:

32817

AN:

152108

Hom.:

3953

Cov.:

AF XY:

0.206

AC XY:

15291

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.266

AC:

11022

AN:

41494

American (AMR)

AF:

0.173

AC:

2649

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1103

AN:

3466

East Asian (EAS)

AF:

0.00174

AC:

AN:

5178

South Asian (SAS)

AF:

0.126

AC:

606

AN:

4824

European-Finnish (FIN)

AF:

0.138

AC:

1463

AN:

10594

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15205

AN:

67968

Other (OTH)

AF:

0.240

AC:

507

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1287

2574

3860

5147

6434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.222

Hom.:

7330

Bravo

AF:

0.220

EpiCase

AF:

0.241

EpiControl

AF:

0.240

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 27, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.028

(source)

DANN

Benign

0.63

PhyloP100

-4.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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