Genetic Variant NM_001385305.1:c.-7+7534T>A (chr20-2955558-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001385305.1(PTPRA):c.-7+7534T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 889,674 control chromosomes in the GnomAD database, including 171 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 0.023 ( 125 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 46 hom. )

Consequence

PTPRA
NM_001385305.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.860

Publications

0 publications found

Variant links:

Genes affected

PTPRA (HGNC:9664): (protein tyrosine phosphatase receptor type A) 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 domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. This PTP has been shown to dephosphorylate and activate Src family tyrosine kinases, and is implicated in the regulation of integrin signaling, cell adhesion and proliferation. Three alternatively spliced variants of this gene, which encode two distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

PTPRA 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=-0.7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385305.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PTPRA	NM_001385305.1	MANE Select	c.-7+7534T>A	intron	N/A	NP_001372234.1
PTPRA	NM_001385302.1		c.28-8714T>A	intron	N/A	NP_001372231.1
PTPRA	NM_001385303.1		c.28-8714T>A	intron	N/A	NP_001372232.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PTPRA	ENST00000399903.7	TSL:5 MANE Select	c.-7+7534T>A	intron	N/A	ENSP00000382787.2
PTPRA	ENST00000216877.10	TSL:1	c.-7+7534T>A	intron	N/A	ENSP00000216877.6
PTPRA	ENST00000356147.3	TSL:1	c.-96-51T>A	intron	N/A	ENSP00000348468.3

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3448

AN:

152224

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0770

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00922

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.00194

AC:

1434

AN:

737332

Hom.:

AF XY:

0.00182

AC XY:

624

AN XY:

342490

show subpopulations

African (AFR)

AF:

0.0833

AC:

1140

AN:

13686

American (AMR)

AF:

0.00703

AC:

AN:

854

Ashkenazi Jewish (ASJ)

AF:

0.0148

AC:

AN:

4600

East Asian (EAS)

AF:

0.00

AC:

AN:

3174

South Asian (SAS)

AF:

0.000138

AC:

AN:

14496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

246

Middle Eastern (MID)

AF:

0.00349

AC:

AN:

1434

European-Non Finnish (NFE)

AF:

0.000120

AC:

AN:

674782

Other (OTH)

AF:

0.00549

AC:

132

AN:

24060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

121

181

242

302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.0226

AC:

3450

AN:

152342

Hom.:

125

Cov.:

AF XY:

0.0214

AC XY:

1598

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.0769

AC:

3196

AN:

41568

American (AMR)

AF:

0.00914

AC:

140

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68030

Other (OTH)

AF:

0.0199

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

165

329

494

658

823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0135

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.86

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over