12-79689946-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002583.4(PAWR):c.299G>A(p.Arg100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,401,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PAWR
NM_002583.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20193905).

BS2

High AC in GnomAd4 at 8 AD gene.

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.299G>A	p.Arg100Gln	missense	Exon 2 of 7	NP_002574.2	Q96IZ0
PAWR	NM_001354732.2		c.299G>A	p.Arg100Gln	missense	Exon 2 of 7	NP_001341661.1	Q96IZ0
PAWR	NM_001354733.2		c.299G>A	p.Arg100Gln	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.299G>A	p.Arg100Gln	missense	Exon 2 of 7	ENSP00000328088.4	Q96IZ0
PAWR	ENST00000903360.1		c.299G>A	p.Arg100Gln	missense	Exon 1 of 6	ENSP00000573419.1
PAWR	ENST00000912080.1		c.299G>A	p.Arg100Gln	missense	Exon 2 of 7	ENSP00000582139.1

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

16652

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1249904

Hom.:

Cov.:

AF XY:

0.00000658

AC XY:

AN XY:

607896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24134

American (AMR)

AF:

0.0000721

AC:

AN:

13866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17538

East Asian (EAS)

AF:

0.00

AC:

AN:

28154

South Asian (SAS)

AF:

0.00

AC:

AN:

57832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1016948

Other (OTH)

AF:

0.0000972

AC:

AN:

51444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.0000527

AC:

AN:

151762

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74118

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41378

American (AMR)

AF:

0.000393

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67870

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000166

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

2.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.60

REVEL

Benign

0.043

Sift

Benign

0.24

Sift4G

Benign

0.58

Polyphen

1.0

Vest4

0.076

MutPred

0.31

Gain of catalytic residue at S95 (P = 0)

MVP

0.24

MPC

0.76

ClinPred

0.65

GERP RS

3.2

PromoterAI

0.097

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.17

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over