rs10773771

Positions:

• chr12-130371771-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000245255.7(PIWIL1):​c.*173C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 405,492 control chromosomes in the GnomAD database, including 63,350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (20909 hom., cov: 32)
  • Exomes 𝑓: 0.58 (42441 hom.)
• Consequence: PIWIL1 ENST00000245255.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIWIL1	NM_004764.5	c.*173C>T		3_prime_UTR_variant	21/21	ENST00000245255.7	NP_004755.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIWIL1	ENST00000245255.7	c.*173C>T		3_prime_UTR_variant	21/21	1	NM_004764.5	ENSP00000245255	P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76953 AN: 151716 Hom.: 20903 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.576 AC: 146028 AN: 253658 Hom.: 42441 Cov.: 3 AF XY: 0.575 AC XY: 75461 AN XY: 131126

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.633

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.510

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.507 AC: 76981 AN: 151834 Hom.: 20909 Cov.: 32 AF XY: 0.509 AC XY: 37762 AN XY: 74208

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.538

Alfa AF: 0.585 Hom.: 53273

Bravo AF: 0.486

Asia WGS AF: 0.609 AC: 2113 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs10773771; hg19: chr12-130856316; COSMIC: COSV105046879; COSMIC: COSV105046879;