Variant 12-79621127-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002583.4(PAWR):c.597T>A(p.Ile199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,607,414 control chromosomes in the GnomAD database, including 480,746 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 34752 hom., cov: 31)

Exomes 𝑓: 0.77 ( 445994 hom. )

Consequence

PAWR
NM_002583.4 synonymous

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=0.128 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAWR	NM_002583.4 linkuse as main transcript	c.597T>A	p.Ile199=	synonymous_variant	3/7	ENST00000328827.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PAWR	ENST00000328827.9 linkuse as main transcript	c.597T>A	p.Ile199=	synonymous_variant	3/7	1	NM_002583.4	P1
PAWR	ENST00000551712.1 linkuse as main transcript	c.435T>A	p.Ile145=	synonymous_variant	2/4	3
PAWR	ENST00000550006.1 linkuse as main transcript	n.481T>A		non_coding_transcript_exon_variant	3/3	3
PAWR	ENST00000549050.1 linkuse as main transcript	n.57+10979T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95751

AN:

152014

Hom.:

34760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.766

Gnomad AMR

AF:

0.724

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.582

Gnomad FIN

AF:

0.814

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.817

Gnomad OTH

AF:

0.672

GnomAD3 exomes

AF:

0.705

AC:

176588

AN:

250542

Hom.:

65706

AF XY:

0.709

AC XY:

96097

AN XY:

135470

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.734

Gnomad ASJ exome

AF:

0.682

Gnomad EAS exome

AF:

0.478

Gnomad SAS exome

AF:

0.590

Gnomad FIN exome

AF:

0.822

Gnomad NFE exome

AF:

0.808

Gnomad OTH exome

AF:

0.733

GnomAD4 exome

AF:

0.773

AC:

1124886

AN:

1455282

Hom.:

445994

Cov.:

AF XY:

0.769

AC XY:

556946

AN XY:

724456

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.734

Gnomad4 ASJ exome

AF:

0.685

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.597

Gnomad4 FIN exome

AF:

0.825

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.729

GnomAD4 genome

AF:

0.629

AC:

95746

AN:

152132

Hom.:

34752

Cov.:

AF XY:

0.629

AC XY:

46813

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.724

Gnomad4 ASJ

AF:

0.679

Gnomad4 EAS

AF:

0.499

Gnomad4 SAS

AF:

0.583

Gnomad4 FIN

AF:

0.814

Gnomad4 NFE

AF:

0.817

Gnomad4 OTH

AF:

0.667

Alfa

AF:

0.491

Hom.:

3958

EpiCase

AF:

0.800

EpiControl

AF:

0.791

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.3

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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