Variant chr9-109389341-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002829.4(PTPN3):c.2145C>T(p.Ile715=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00939 in 1,613,942 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0096 ( 108 hom. )

Consequence

PTPN3
NM_002829.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.143

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 9-109389341-G-A is Benign according to our data. Variant chr9-109389341-G-A is described in ClinVar as [Benign]. Clinvar id is 707948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.143 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN3	NM_002829.4 linkuse as main transcript	c.2145C>T	p.Ile715=	synonymous_variant	22/26	ENST00000374541.4	NP_002820.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN3	ENST00000374541.4 linkuse as main transcript	c.2145C>T	p.Ile715=	synonymous_variant	22/26	5	NM_002829.4	ENSP00000363667	P1	P26045-1

Frequencies

GnomAD3 genomes

AF:

0.00711

AC:

1083

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00867

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00655

AC:

1645

AN:

251074

Hom.:

AF XY:

0.00682

AC XY:

925

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00206

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00833

GnomAD4 exome

AF:

0.00962

AC:

14066

AN:

1461604

Hom.:

108

Cov.:

AF XY:

0.00943

AC XY:

6860

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00203

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00722

GnomAD4 genome

AF:

0.00711

AC:

1083

AN:

152338

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

506

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00867

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00978

Hom.:

Bravo

AF:

0.00622

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00927

EpiControl

AF:

0.0104

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.6

DANN

Benign

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over