Variant chr12-130357093-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004764.5(PIWIL1):c.1580G>A(p.Arg527Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0661 in 1,608,668 control chromosomes in the GnomAD database, including 4,817 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.056 ( 364 hom., cov: 33)

Exomes 𝑓: 0.067 ( 4453 hom. )

Consequence

PIWIL1
NM_004764.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

PIWIL1 (HGNC:9007): (piwi like RNA-mediated gene silencing 1) This gene encodes a member of the PIWI subfamily of Argonaute proteins, evolutionarily conserved proteins containing both PAZ and Piwi motifs that play important roles in stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. The encoded protein may play a role as an intrinsic regulator of the self-renewal capacity of germline and hematopoietic stem cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

PIWIL1 links:

PIWIL1 (HGNC:):

PIWIL1 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 (MetaRNN=0.0011547804).

BP6

Variant 12-130357093-G-A is Benign according to our data. Variant chr12-130357093-G-A is described in ClinVar as [Benign]. Clinvar id is 3055830.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIWIL1	NM_004764.5 linkuse as main transcript	c.1580G>A	p.Arg527Lys	missense_variant	13/21	ENST00000245255.7	NP_004755.2	Q96J94-1A0A024RBS5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIWIL1	ENST00000245255.7 linkuse as main transcript	c.1580G>A	p.Arg527Lys	missense_variant	13/21	1	NM_004764.5	ENSP00000245255.3		Q96J94-1

Frequencies

GnomAD3 genomes

AF:

0.0561

AC:

8543

AN:

152154

Hom.:

367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0395

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.0551

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0618

Gnomad OTH

AF:

0.0511

GnomAD3 exomes

AF:

0.0740

AC:

18425

AN:

249136

Hom.:

1026

AF XY:

0.0810

AC XY:

10921

AN XY:

134744

show subpopulations

Gnomad AFR exome

AF:

0.0274

Gnomad AMR exome

AF:

0.0236

Gnomad ASJ exome

AF:

0.0370

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.0575

Gnomad NFE exome

AF:

0.0621

Gnomad OTH exome

AF:

0.0638

GnomAD4 exome

AF:

0.0671

AC:

97729

AN:

1456396

Hom.:

4453

Cov.:

AF XY:

0.0712

AC XY:

51552

AN XY:

723560

show subpopulations

Gnomad4 AFR exome

AF:

0.0264

Gnomad4 AMR exome

AF:

0.0243

Gnomad4 ASJ exome

AF:

0.0367

Gnomad4 EAS exome

AF:

0.134

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.0628

Gnomad4 NFE exome

AF:

0.0588

Gnomad4 OTH exome

AF:

0.0680

GnomAD4 genome

AF:

0.0560

AC:

8529

AN:

152272

Hom.:

364

Cov.:

AF XY:

0.0592

AC XY:

4406

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0281

Gnomad4 AMR

AF:

0.0346

Gnomad4 ASJ

AF:

0.0395

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.0551

Gnomad4 NFE

AF:

0.0618

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0616

Hom.:

832

Bravo

AF:

0.0493

TwinsUK

AF:

0.0566

AC:

210

ALSPAC

AF:

0.0592

AC:

228

ESP6500AA

AF:

0.0291

AC:

128

ESP6500EA

AF:

0.0571

AC:

491

ExAC

AF:

0.0779

AC:

9455

Asia WGS

AF:

0.154

AC:

536

AN:

3478

EpiCase

AF:

0.0601

EpiControl

AF:

0.0589

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PIWIL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.034

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.23

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.69

PrimateAI

Benign

0.43

PROVEAN

Benign

0.28

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

0.97

Polyphen

0.0

Vest4

0.015

MPC

0.61

ClinPred

0.012

GERP RS

4.3

Varity_R

0.066

gMVP

0.34

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over