Genetic Variant PAWR:p.Pro42Arg (chr12-79690120-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002583.4(PAWR):c.125C>G(p.Pro42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAWR
NM_002583.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.201

Publications

0 publications found

Variant links:

Genes affected

PAWR (HGNC:8614): (pro-apoptotic WT1 regulator) This gene encodes a tumor suppressor protein that selectively induces apoptosis in cancer cells through intracellular and extracellular mechanisms. The intracellular mechanism involves the inhibition of pro-survival pathways and the activation of Fas-mediated apoptosis, while the extracellular mechanism involves the binding of a secreted form of this protein to glucose regulated protein 78 (GRP78) on the cell surface, which leads to activation of the extrinsic apoptotic pathway. This gene is located on the unstable human chromosomal 12q21 region and is often deleted or mutated different tumors. The encoded protein also plays an important role in the progression of age-related diseases. [provided by RefSeq, Aug 2017]

PAWR links:

PPP1R12A-AS2 (HGNC:55456): (PPP1R12A antisense RNA 2)

PPP1R12A-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1559313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002583.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAWR	NM_002583.4	MANE Select	c.125C>G	p.Pro42Arg	missense	Exon 2 of 7	NP_002574.2	Q96IZ0
PAWR	NM_001354732.2		c.125C>G	p.Pro42Arg	missense	Exon 2 of 7	NP_001341661.1	Q96IZ0
PAWR	NM_001354733.2		c.125C>G	p.Pro42Arg	missense	Exon 2 of 5	NP_001341662.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAWR	ENST00000328827.9	TSL:1 MANE Select	c.125C>G	p.Pro42Arg	missense	Exon 2 of 7	ENSP00000328088.4	Q96IZ0
PAWR	ENST00000903360.1		c.125C>G	p.Pro42Arg	missense	Exon 1 of 6	ENSP00000573419.1
PAWR	ENST00000912080.1		c.125C>G	p.Pro42Arg	missense	Exon 2 of 7	ENSP00000582139.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1335048

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

659090

African (AFR)

AF:

0.00

AC:

AN:

27124

American (AMR)

AF:

0.00

AC:

AN:

30676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23560

East Asian (EAS)

AF:

0.00

AC:

AN:

29908

South Asian (SAS)

AF:

0.00

AC:

AN:

75798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5024

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1050284

Other (OTH)

AF:

0.00

AC:

AN:

55506

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.27

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.45

M_CAP

Benign

0.021

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

0.20

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.30

REVEL

Benign

0.016

Sift

Benign

0.10

Sift4G

Benign

0.17

Polyphen

0.60

Vest4

0.093

MutPred

0.26

Gain of catalytic residue at G43 (P = 0.0024)

MVP

0.42

MPC

0.50

ClinPred

0.31

GERP RS

2.5

PromoterAI

-0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.20

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over