Variant rs10848087 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004764.5(PIWIL1):c.1128G>A(p.Leu376=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,607,994 control chromosomes in the GnomAD database, including 28,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 2786 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25328 hom. )

Consequence

PIWIL1
NM_004764.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0280

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

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

BP6

Variant 12-130354620-G-A is Benign according to our data. Variant chr12-130354620-G-A is described in ClinVar as [Benign]. Clinvar id is 3060640.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.028 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIWIL1	NM_004764.5 linkuse as main transcript	c.1128G>A	p.Leu376=	synonymous_variant	10/21	ENST00000245255.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIWIL1	ENST00000245255.7 linkuse as main transcript	c.1128G>A	p.Leu376=	synonymous_variant	10/21	1	NM_004764.5	P1	Q96J94-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28383

AN:

151968

Hom.:

2771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.173

AC:

42317

AN:

244828

Hom.:

3957

AF XY:

0.178

AC XY:

23534

AN XY:

132460

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0976

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.184

AC:

267733

AN:

1455908

Hom.:

25328

Cov.:

AF XY:

0.185

AC XY:

134125

AN XY:

724242

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.217

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.186

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.187

AC:

28425

AN:

152086

Hom.:

2786

Cov.:

AF XY:

0.184

AC XY:

13703

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.258

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.189

Hom.:

3560

Bravo

AF:

0.187

Asia WGS

AF:

0.216

AC:

750

AN:

3478

EpiCase

AF:

0.183

EpiControl

AF:

0.188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PIWIL1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.1

DANN

Benign

0.69

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