chr7-77611018-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002835.4(PTPN12):c.911A>G(p.His304Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

PTPN12
NM_002835.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 1.27

Publications

3 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013361752).

BS2

High AC in GnomAd4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002835.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN12	NM_002835.4	MANE Select	c.911A>G	p.His304Arg	missense	Exon 11 of 18	NP_002826.3
PTPN12	NM_001131008.2		c.554A>G	p.His185Arg	missense	Exon 11 of 18	NP_001124480.1	Q05209-3
PTPN12	NM_001131009.2		c.521A>G	p.His174Arg	missense	Exon 10 of 17	NP_001124481.1	Q05209-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN12	ENST00000248594.11	TSL:1 MANE Select	c.911A>G	p.His304Arg	missense	Exon 11 of 18	ENSP00000248594.6	Q05209-1
PTPN12	ENST00000962769.1		c.908A>G	p.His303Arg	missense	Exon 11 of 18	ENSP00000632828.1
PTPN12	ENST00000962770.1		c.740A>G	p.His247Arg	missense	Exon 8 of 15	ENSP00000632829.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000159

AC:

AN:

251202

AF XY:

0.000125

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.0000705

AC:

103

AN:

1460890

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

726786

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00283

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

86126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111488

Other (OTH)

AF:

0.000199

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

PTPN12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.11

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.61

M_CAP

Benign

0.0039

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

1.3

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.84

REVEL

Benign

0.093

Sift

Benign

0.39

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.11

MVP

0.18

MPC

0.026

ClinPred

0.025

GERP RS

4.3

Varity_R

0.042

gMVP

0.42

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over