rs10773771

Variant names:

• chr12-130371771-C-T
• rs10773771
• NM_004764.5:c.*173C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004764.5(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 NM_004764.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PIWIL1	NM_004764.5	c.*173C>T		3_prime_UTR_variant	Exon 21 of 21	ENST00000245255.7	NP_004755.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIWIL1	ENST00000245255.7	c.*173C>T		3_prime_UTR_variant	Exon 21 of 21	1	NM_004764.5	ENSP00000245255.3

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

African (AFR) AF: 0.291 AC: 1984 AN: 6814

American (AMR) AF: 0.456 AC: 4139 AN: 9086

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 5505 AN: 8700

East Asian (EAS) AF: 0.621 AC: 12565 AN: 20222

South Asian (SAS) AF: 0.510 AC: 6189 AN: 12126

European-Finnish (FIN) AF: 0.592 AC: 11002 AN: 18586

Middle Eastern (MID) AF: 0.614 AC: 761 AN: 1240

European-Non Finnish (NFE) AF: 0.590 AC: 94906 AN: 160926

Other (OTH) AF: 0.563 AC: 8977 AN: 15958

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

African (AFR) AF: 0.301 AC: 12465 AN: 41372

American (AMR) AF: 0.486 AC: 7416 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2214 AN: 3462

East Asian (EAS) AF: 0.635 AC: 3280 AN: 5166

South Asian (SAS) AF: 0.567 AC: 2732 AN: 4816

European-Finnish (FIN) AF: 0.614 AC: 6439 AN: 10482

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40640 AN: 67954

Other (OTH) AF: 0.538 AC: 1132 AN: 2106

Alfa AF: 0.572 Hom.: 106674

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
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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