Variant 7-77571075-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_002835.4(PTPN12):c.100-3A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,526,904 control chromosomes in the GnomAD database, including 60,545 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.26 ( 5405 hom., cov: 33)

Exomes 𝑓: 0.28 ( 55140 hom. )

Consequence

PTPN12
NM_002835.4 splice_region, intron

Scores

Splicing: ADA: 0.002689

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.60

Variant links:

Genes affected

PTPN12 (HGNC:9645): (protein tyrosine phosphatase non-receptor type 12) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains a C-terminal PEST motif, which serves as a protein-protein interaction domain, and may regulate protein intracellular half-life. This PTP was found to bind and dephosphorylate the product of the oncogene c-ABL and thus may play a role in oncogenesis. This PTP was also shown to interact with, and dephosphorylate, various products related to cytoskeletal structure and cell adhesion, such as p130 (Cas), CAKbeta/PTK2B, PSTPIP1, and paxillin. This suggests it has a regulatory role in controlling cell shape and mobility. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

PTPN12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 7-77571075-A-T is Benign according to our data. Variant chr7-77571075-A-T is described in ClinVar as [Benign]. Clinvar id is 3059642.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN12	NM_002835.4 link	c.100-3A>T		splice_region_variant, intron_variant		ENST00000248594.11	NP_002826.3	Q05209-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN12	ENST00000248594.11 link	c.100-3A>T		splice_region_variant, intron_variant		1	NM_002835.4	ENSP00000248594.6		Q05209-1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40176

AN:

151946

Hom.:

5394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.266

GnomAD3 exomes

AF:

0.263

AC:

52056

AN:

197720

Hom.:

6932

AF XY:

0.263

AC XY:

28607

AN XY:

108730

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.156

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.281

AC:

386420

AN:

1374842

Hom.:

55140

Cov.:

AF XY:

0.280

AC XY:

191997

AN XY:

685490

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.253

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.265

AC:

40223

AN:

152062

Hom.:

5405

Cov.:

AF XY:

0.260

AC XY:

19325

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.271

Hom.:

1776

Bravo

AF:

0.264

Asia WGS

AF:

0.242

AC:

841

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PTPN12-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0027

dbscSNV1_RF

Benign

0.012

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