Genetic Variant PTPN3:c.1002-1505T>C (chr9-109424357-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002829.4(PTPN3):c.1002-1505T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 152,296 control chromosomes in the GnomAD database, including 121 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 0.030 ( 121 hom., cov: 33)

Consequence

PTPN3
NM_002829.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.661

Publications

2 publications found

Variant links:

Genes affected

PTPN3 (HGNC:9655): (protein tyrosine phosphatase non-receptor type 3) 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 protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. P97, a cell cycle regulator involved in a variety of membrane related functions, has been shown to be a substrate of this PTP. This PTP was also found to interact with, and be regulated by adaptor protein 14-3-3 beta. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

PTPN3 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PTPN3 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN3	NM_002829.4 link	c.1002-1505T>C		intron_variant	Intron 12 of 25	ENST00000374541.4	NP_002820.3	P26045-1B7Z9V1Q8N4S3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPN3	ENST00000374541.4 link	c.1002-1505T>C	intron_variant	Intron 12 of 25	5	NM_002829.4	ENSP00000363667.1	P26045-1
PTPN3	ENST00000412145.5 link	c.609-1505T>C	intron_variant	Intron 7 of 20	1		ENSP00000416654.1	P26045-2
PTPN3	ENST00000446349.5 link	c.608+2593T>C	intron_variant	Intron 7 of 19	1		ENSP00000395384.1	P26045-3
PTPN3	ENST00000262539.7 link	c.1002-1505T>C	intron_variant	Intron 12 of 25	5		ENSP00000262539.4	J3KN34

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4541

AN:

152178

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00572

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0732

Gnomad ASJ

AF:

0.0462

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.0242

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0421

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

GnomAD4 genome

AF:

0.0299

AC:

4548

AN:

152296

Hom.:

121

Cov.:

AF XY:

0.0314

AC XY:

2339

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00570

AC:

237

AN:

41578

American (AMR)

AF:

0.0733

AC:

1121

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0462

AC:

160

AN:

3466

East Asian (EAS)

AF:

0.151

AC:

782

AN:

5172

South Asian (SAS)

AF:

0.0251

AC:

121

AN:

4826

European-Finnish (FIN)

AF:

0.0183

AC:

194

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0270

AC:

1834

AN:

68020

Other (OTH)

AF:

0.0421

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

225

450

676

901

1126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0293

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.0660

AC:

229

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.45

(source)

DANN

Benign

0.83

PhyloP100

-0.66

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