Variant 7-77618504-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002835.4(PTPN12):c.964G>C(p.Val322Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 1,450,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V322I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

PTPN12
NM_002835.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16117147).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN12	NM_002835.4 linkuse as main transcript	c.964G>C	p.Val322Leu	missense_variant	12/18	ENST00000248594.11	NP_002826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN12	ENST00000248594.11 linkuse as main transcript	c.964G>C	p.Val322Leu	missense_variant	12/18	1	NM_002835.4	ENSP00000248594	P1	Q05209-1
PTPN12	ENST00000415482.6 linkuse as main transcript	c.607G>C	p.Val203Leu	missense_variant	12/18	5		ENSP00000392429		Q05209-3
PTPN12	ENST00000435495.6 linkuse as main transcript	c.574G>C	p.Val192Leu	missense_variant	11/17	2		ENSP00000397991		Q05209-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248078

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000690

AC:

AN:

1450264

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

721624

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000815

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000369

Hom.:

52116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.23

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.0080

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.91

P;P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.60

N;N;N

REVEL

Benign

0.019

Sift

Benign

0.037

D;D;D

Sift4G

Benign

0.68

T;T;T

Polyphen

0.0090

B;.;.

Vest4

0.25

MutPred

0.24

Gain of relative solvent accessibility (P = 0.0275);.;.;

MVP

0.26

MPC

0.024

ClinPred

0.19

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over