Variant 15-75469787-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002833.4(PTPN9):c.1567+5C>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,612,210 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 19 hom. )

Consequence

PTPN9
NM_002833.4 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.0002129

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.37

Variant links:

Genes affected

PTPN9 (HGNC:9661): (protein tyrosine phosphatase non-receptor type 9) 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 N-terminal domain that shares a significant similarity with yeast SEC14, which is a protein that has phosphatidylinositol transfer activity and is required for protein secretion through the Golgi complex in yeast. This PTP was found to be activated by polyphosphoinositide, and is thought to be involved in signaling events regulating phagocytosis. [provided by RefSeq, Jul 2008]

PTPN9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 15-75469787-G-A is Benign according to our data. Variant chr15-75469787-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 506 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN9	NM_002833.4 linkuse as main transcript	c.1567+5C>T		splice_donor_5th_base_variant, intron_variant		ENST00000618819.5	NP_002824.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
PTPN9	ENST00000618819.5 linkuse as main transcript	c.1567+5C>T	splice_donor_5th_base_variant, intron_variant	1	NM_002833.4	ENSP00000482732	P1
PTPN9	ENST00000568108.1 linkuse as main transcript	n.438+5C>T	splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant	2
PTPN9	ENST00000563835.1 linkuse as main transcript		downstream_gene_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00332

AC:

506

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00569

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00335

AC:

841

AN:

250990

Hom.:

AF XY:

0.00346

AC XY:

470

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.00547

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00501

AC:

7310

AN:

1459880

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

3500

AN XY:

726248

show subpopulations

Gnomad4 AFR exome

AF:

0.000898

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000720

Gnomad4 FIN exome

AF:

0.00206

Gnomad4 NFE exome

AF:

0.00592

Gnomad4 OTH exome

AF:

0.00571

GnomAD4 genome

AF:

0.00332

AC:

506

AN:

152330

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00569

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00414

Hom.:

Bravo

AF:

0.00343

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00600

EpiControl

AF:

0.00551

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

PTPN9: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.90

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.0

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

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