Variant chr12-79621127-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002583.4(PAWR):c.597T>G(p.Ile199Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,608,512 control chromosomes in the GnomAD database, including 22,372 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.23 ( 10850 hom., cov: 31)

Exomes 𝑓: 0.049 ( 11522 hom. )

Consequence

PAWR
NM_002583.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.128

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:

PAWR (HGNC:):

PAWR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2461969E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAWR	NM_002583.4 linkuse as main transcript	c.597T>G	p.Ile199Met	missense_variant	3/7	ENST00000328827.9	NP_002574.2	Q96IZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PAWR	ENST00000328827.9 linkuse as main transcript	c.597T>G	p.Ile199Met	missense_variant	3/7	1	NM_002583.4	ENSP00000328088.4	Q96IZ0
PAWR	ENST00000551712.1 linkuse as main transcript	c.432T>G	p.Ile144Met	missense_variant	2/4	3		ENSP00000448317.1	H0YI16
PAWR	ENST00000550006.1 linkuse as main transcript	n.481T>G		non_coding_transcript_exon_variant	3/3	3
PAWR	ENST00000549050.1 linkuse as main transcript	n.57+10979T>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34865

AN:

152042

Hom.:

10799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.706

Gnomad AMI

AF:

0.0736

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0671

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.0914

Gnomad FIN

AF:

0.0201

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.105

AC:

26214

AN:

250542

Hom.:

5231

AF XY:

0.0904

AC XY:

12241

AN XY:

135470

show subpopulations

Gnomad AFR exome

AF:

0.722

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.0633

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.0849

Gnomad FIN exome

AF:

0.0193

Gnomad NFE exome

AF:

0.0196

Gnomad OTH exome

AF:

0.0682

GnomAD4 exome

AF:

0.0491

AC:

71481

AN:

1456352

Hom.:

11522

Cov.:

AF XY:

0.0479

AC XY:

34736

AN XY:

724916

show subpopulations

Gnomad4 AFR exome

AF:

0.733

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.0656

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.0849

Gnomad4 FIN exome

AF:

0.0184

Gnomad4 NFE exome

AF:

0.0155

Gnomad4 OTH exome

AF:

0.0853

GnomAD4 genome

AF:

0.230

AC:

34971

AN:

152160

Hom.:

10850

Cov.:

AF XY:

0.225

AC XY:

16712

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.706

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0671

Gnomad4 EAS

AF:

0.214

Gnomad4 SAS

AF:

0.0905

Gnomad4 FIN

AF:

0.0201

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.0540

Hom.:

3958

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.655

AC:

2888

ESP6500EA

AF:

0.0149

AC:

128

ExAC

AF:

0.115

AC:

13979

EpiCase

AF:

0.0213

EpiControl

AF:

0.0225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.9

DANN

Benign

0.12

DEOGEN2

Benign

0.20

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.071

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.76

PrimateAI

Benign

0.40

PROVEAN

Benign

0.12

REVEL

Benign

0.066

Sift

Benign

1.0

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.028

MPC

0.42

ClinPred

0.0015

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.023

gMVP

0.050

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

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