Variant 12-79592625-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002583.4(PAWR):c.1005G>T(p.Val335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0075 in 769,000 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 148 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 66 hom. )

Consequence

PAWR
NM_002583.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.984

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 12-79592625-C-A is Benign according to our data. Variant chr12-79592625-C-A is described in ClinVar as [Benign]. Clinvar id is 779530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.984 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PAWR	NM_002583.4 linkuse as main transcript	c.1005G>T	p.Val335=	synonymous_variant	7/7	ENST00000328827.9	NP_002574.2
PAWR	NM_001354732.2 linkuse as main transcript	c.1005G>T	p.Val335=	synonymous_variant	7/7		NP_001341661.1
PAWR	XM_047428916.1 linkuse as main transcript	c.1005G>T	p.Val335=	synonymous_variant	6/6		XP_047284872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAWR	ENST00000328827.9 linkuse as main transcript	c.1005G>T	p.Val335=	synonymous_variant	7/7	1	NM_002583.4	ENSP00000328088	P1

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3560

AN:

151778

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0814

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000486

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00687

AC:

1634

AN:

237986

Hom.:

AF XY:

0.00550

AC XY:

710

AN XY:

129004

show subpopulations

Gnomad AFR exome

AF:

0.0834

Gnomad AMR exome

AF:

0.00358

Gnomad ASJ exome

AF:

0.00242

Gnomad EAS exome

AF:

0.0000567

Gnomad SAS exome

AF:

0.00426

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000313

Gnomad OTH exome

AF:

0.00356

GnomAD4 exome

AF:

0.00352

AC:

2173

AN:

617108

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

1084

AN XY:

336616

show subpopulations

Gnomad4 AFR exome

AF:

0.0800

Gnomad4 AMR exome

AF:

0.00388

Gnomad4 ASJ exome

AF:

0.00269

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00414

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.000253

Gnomad4 OTH exome

AF:

0.00685

GnomAD4 genome

AF:

0.0237

AC:

3598

AN:

151892

Hom.:

148

Cov.:

AF XY:

0.0234

AC XY:

1739

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0820

Gnomad4 AMR

AF:

0.00746

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000486

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.00512

Hom.:

Bravo

AF:

0.0278

Asia WGS

AF:

0.00665

AC:

AN:

3474

EpiCase

AF:

0.000273

EpiControl

AF:

0.000654

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

4.8

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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