Variant 7-77600660-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_002835.4(PTPN12):c.553-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00902 in 1,576,236 control chromosomes in the GnomAD database, including 73 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 0.0064 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 65 hom. )

Consequence

PTPN12
NM_002835.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001136

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.173

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 7-77600660-G-A is Benign according to our data. Variant chr7-77600660-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024795.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 964 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN12	NM_002835.4 linkuse as main transcript	c.553-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000248594.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN12	ENST00000248594.11 linkuse as main transcript	c.553-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002835.4	P1	Q05209-1

Frequencies

GnomAD3 genomes

AF:

0.00635

AC:

962

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00310

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00480

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00953

Gnomad OTH

AF:

0.00528

GnomAD3 exomes

AF:

0.00622

AC:

1357

AN:

218014

Hom.:

AF XY:

0.00655

AC XY:

775

AN XY:

118280

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00166

Gnomad ASJ exome

AF:

0.00799

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00453

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.00847

Gnomad OTH exome

AF:

0.00553

GnomAD4 exome

AF:

0.00930

AC:

13247

AN:

1424504

Hom.:

Cov.:

AF XY:

0.00914

AC XY:

6465

AN XY:

707374

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00203

Gnomad4 ASJ exome

AF:

0.00857

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.00558

Gnomad4 FIN exome

AF:

0.00901

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.00796

GnomAD4 genome

AF:

0.00635

AC:

964

AN:

151732

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

472

AN XY:

74124

show subpopulations

Gnomad4 AFR

AF:

0.00196

Gnomad4 AMR

AF:

0.00310

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00522

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.00953

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00780

Hom.:

Bravo

AF:

0.00579

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

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

Jan 01, 2024

PTPN12: BP4, BS2 -

PTPN12-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 13, 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

-0.64

CADD

Benign

6.1

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0040

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