Variant 12-79690184-C-G 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_002583.4(PAWR):c.61G>C(p.Glu21Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000355 in 1,533,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

PAWR
NM_002583.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1871657).

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAWR	NM_002583.4 linkuse as main transcript	c.61G>C	p.Glu21Gln	missense_variant	2/7	ENST00000328827.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PAWR	ENST00000328827.9 linkuse as main transcript	c.61G>C	p.Glu21Gln	missense_variant	2/7	1	NM_002583.4	P1
PPP1R12A-AS2	ENST00000551995.1 linkuse as main transcript	n.41C>G		non_coding_transcript_exon_variant	1/2	5
PAWR	ENST00000548426.1 linkuse as main transcript	c.61G>C	p.Glu21Gln	missense_variant	2/2	3
PAWR	ENST00000552637.1 linkuse as main transcript	c.61G>C	p.Glu21Gln	missense_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000184

AC:

AN:

130152

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

72352

show subpopulations

Gnomad AFR exome

AF:

0.000209

Gnomad AMR exome

AF:

0.0000405

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:

0.000457

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000369

AC:

510

AN:

1381382

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

258

AN XY:

682796

show subpopulations

Gnomad4 AFR exome

AF:

0.0000338

Gnomad4 AMR exome

AF:

0.0000277

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:

0.000456

Gnomad4 OTH exome

AF:

0.000295

GnomAD4 genome

AF:

0.000224

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000383

Gnomad4 OTH

AF:

0.000961

Alfa

AF:

0.000306

Hom.:

Bravo

AF:

0.000264

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.61G>C (p.E21Q) alteration is located in exon 2 (coding exon 1) of the PAWR gene. This alteration results from a G to C substitution at nucleotide position 61, causing the glutamic acid (E) at amino acid position 21 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.47

T;T;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.095

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.84

T;D;D

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.3

N;D;D

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.064

T;.;.

Polyphen

0.99

D;.;.

Vest4

0.37

MVP

0.75

MPC

1.1

ClinPred

0.16

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.54

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

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