Genetic Variant NM_002583.4:c.*513T>G (chr12-79592094-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002583.4(PAWR):c.*513T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,506 control chromosomes in the GnomAD database, including 15,397 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 0.35 ( 15396 hom., cov: 32)

Exomes 𝑓: 0.090 ( 1 hom. )

Consequence

PAWR
NM_002583.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.235

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PAWR	NM_002583.4 link	c.*513T>G	3_prime_UTR_variant	Exon 7 of 7	ENST00000328827.9	NP_002574.2	Q96IZ0
PAWR	NM_001354732.2 link	c.*513T>G	3_prime_UTR_variant	Exon 7 of 7		NP_001341661.1
PAWR	XM_047428916.1 link	c.*513T>G	3_prime_UTR_variant	Exon 6 of 6		XP_047284872.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PAWR	ENST00000328827.9 link	c.*513T>G	3_prime_UTR_variant	Exon 7 of 7	1	NM_002583.4	ENSP00000328088.4	Q96IZ0
PAWR	ENST00000550603.1 link	c.212+517T>G	intron_variant	Intron 3 of 3	5		ENSP00000447507.1	H0YHP5
PAWR	ENST00000548075.5 link	n.503+517T>G	intron_variant	Intron 4 of 4	4
PAWR	ENST00000549050.1 link	n.58-1813T>G	intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52666

AN:

151934

Hom.:

15340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.801

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.0938

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.0903

AC:

AN:

454

Hom.:

Cov.:

AF XY:

0.0956

AC XY:

AN XY:

272

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0869

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.136

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.347

AC:

52779

AN:

152052

Hom.:

15396

Cov.:

AF XY:

0.339

AC XY:

25221

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.801

AC:

33244

AN:

41478

American (AMR)

AF:

0.249

AC:

3813

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

890

AN:

3470

East Asian (EAS)

AF:

0.299

AC:

1543

AN:

5168

South Asian (SAS)

AF:

0.203

AC:

980

AN:

4828

European-Finnish (FIN)

AF:

0.0938

AC:

994

AN:

10596

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.153

AC:

10417

AN:

67910

Other (OTH)

AF:

0.318

AC:

671

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1141

2281

3422

4562

5703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.273

Hom.:

2300

Bravo

AF:

0.381

Asia WGS

AF:

0.290

AC:

1005

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.7

(source)

DANN

Benign

0.73

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over