Variant 12-130343005-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004764.5(PIWIL1):c.94T>G(p.Tyr32Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,613,930 control chromosomes in the GnomAD database, including 54 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 Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y32C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0097 ( 25 hom., cov: 33)

Exomes 𝑓: 0.00099 ( 29 hom. )

Consequence

PIWIL1
NM_004764.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.67

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026398003).

BP6

Variant 12-130343005-T-G is Benign according to our data. Variant chr12-130343005-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3056689.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00973 (1482/152344) while in subpopulation AFR AF= 0.034 (1415/41576). AF 95% confidence interval is 0.0326. There are 25 homozygotes in gnomad4. There are 696 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIWIL1	NM_004764.5 linkuse as main transcript	c.94T>G	p.Tyr32Asp	missense_variant	3/21	ENST00000245255.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIWIL1	ENST00000245255.7 linkuse as main transcript	c.94T>G	p.Tyr32Asp	missense_variant	3/21	1	NM_004764.5	P1	Q96J94-1

Frequencies

GnomAD3 genomes

AF:

0.00968

AC:

1474

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00255

AC:

642

AN:

251442

Hom.:

AF XY:

0.00176

AC XY:

239

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0349

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000991

AC:

1448

AN:

1461586

Hom.:

Cov.:

AF XY:

0.000884

AC XY:

643

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0360

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00973

AC:

1482

AN:

152344

Hom.:

Cov.:

AF XY:

0.00934

AC XY:

696

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0340

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.0113

ESP6500AA

AF:

0.0338

AC:

149

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00310

AC:

376

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PIWIL1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as likely 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

0.095

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.027

T;T;T;.;T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.33

MetaRNN

Benign

0.0026

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

N;.;.;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.29

N;N;N;N;N;N

REVEL

Benign

0.051

Sift

Benign

0.20

T;T;T;T;T;T

Sift4G

Benign

0.63

T;T;T;T;T;T

Polyphen

0.62

P;.;.;.;.;.

Vest4

0.42

MVP

0.53

MPC

1.9

ClinPred

0.013

GERP RS

3.9

Varity_R

0.083

gMVP

0.43

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