12-130346361-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• 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 criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380

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]

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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	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	c.317-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004764.5	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26042 AN: 151974 Hom.: 2416 Cov.: 33

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

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.: 30 AF XY: 0.164 AC XY: 118296 AN XY: 720288

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.: 33 AF XY: 0.170 AC XY: 12657 AN XY: 74336

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: criteria provided, single submitter

Submissions by phenotype

PIWIL1-related disorder Benign:1

Benign, criteria provided, single submitter

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

Other links and lift over

dbSNP: rs11060836; hg19: chr12-130830906; COSMIC: COSV55350213; COSMIC: COSV55350213;