Variant chr12-79690240-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002583.4(PAWR):c.5C>T(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000147 in 1,358,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PAWR
NM_002583.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAWR	NM_002583.4 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	2/7	ENST00000328827.9	NP_002574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PAWR	ENST00000328827.9 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	2/7	1	NM_002583.4	ENSP00000328088	P1
PPP1R12A-AS2	ENST00000551995.1 linkuse as main transcript	n.97G>A		non_coding_transcript_exon_variant	1/2	5
PAWR	ENST00000548426.1 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	2/2	3		ENSP00000447454
PAWR	ENST00000552637.1 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	2/2	2		ENSP00000449928

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1358280

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

670906

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000188

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 10, 2022

The c.5C>T (p.A2V) alteration is located in exon 2 (coding exon 1) of the PAWR gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). 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

0.98

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

D;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.67

T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.7

N;D;D

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0080

D;.;.

Polyphen

1.0

D;.;.

Vest4

0.57

MutPred

0.36

Gain of catalytic residue at T3 (P = 0.0019);Gain of catalytic residue at T3 (P = 0.0019);Gain of catalytic residue at T3 (P = 0.0019);

MVP

0.66

MPC

0.97

ClinPred

0.98

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.66

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over