Variant chr12-130346361-C-T 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.317-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,600,438 control chromosomes in the GnomAD database, including 22,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.17 ( 2423 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19698 hom. )

Consequence

PIWIL1
NM_004764.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001682

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0380

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 (BayesDel_noAF=-0.79).

BP6

Variant 12-130346361-C-T is Benign according to our data. Variant chr12-130346361-C-T is described in ClinVar as [Benign]. Clinvar id is 3060310.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 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.317-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000245255.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIWIL1	ENST00000245255.7 linkuse as main transcript	c.317-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004764.5	P1	Q96J94-1

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

26042

AN:

151974

Hom.:

2416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.0932

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.155

AC:

38025

AN:

245934

Hom.:

3255

AF XY:

0.161

AC XY:

21336

AN XY:

132788

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.0758

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.0815

Gnomad SAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.162

AC:

234651

AN:

1448346

Hom.:

19698

Cov.:

AF XY:

0.164

AC XY:

118296

AN XY:

720288

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.0819

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.0865

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.171

AC:

26066

AN:

152092

Hom.:

2423

Cov.:

AF XY:

0.170

AC XY:

12657

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.0931

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.162

Hom.:

2381

Bravo

AF:

0.167

Asia WGS

AF:

0.210

AC:

730

AN:

3478

EpiCase

AF:

0.154

EpiControl

AF:

0.159

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

Nov 11, 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

-0.79

CADD

Benign

1.7

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0017

dbscSNV1_RF

Benign

0.054

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