rs1106042

Variant names:

• chr12-130357093-G-A
• rs1106042
• NM_004764.5:c.1580G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004764.5(PIWIL1):​c.1580G>A​(p.Arg527Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0661 in 1,608,668 control chromosomes in the GnomAD database, including 4,817 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.056 (364 hom., cov: 33)
  • Exomes 𝑓: 0.067 (4453 hom.)
• Consequence: PIWIL1 NM_004764.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.23
• Publications: 30 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011547804).
• BP6: Variant 12-130357093-G-A is Benign according to our data. Variant chr12-130357093-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055830.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004764.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIWIL1	NM_004764.5	MANE Select	c.1580G>A	p.Arg527Lys	missense	Exon 13 of 21	NP_004755.2	Q96J94-1
	PIWIL1	NM_001190971.2		c.1580G>A	p.Arg527Lys	missense	Exon 13 of 20	NP_001177900.1	Q96J94-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIWIL1	ENST00000245255.7	TSL:1 MANE Select	c.1580G>A	p.Arg527Lys	missense	Exon 13 of 21	ENSP00000245255.3	Q96J94-1

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8543 AN: 152154 Hom.: 367 Cov.: 33

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0511

GnomAD2 exomes AF: 0.0740 AC: 18425 AN: 249136 AF XY: 0.0810

Gnomad AFR exome AF: 0.0274

Gnomad AMR exome AF: 0.0236

Gnomad ASJ exome AF: 0.0370

Gnomad EAS exome AF: 0.121

Gnomad FIN exome AF: 0.0575

Gnomad NFE exome AF: 0.0621

Gnomad OTH exome AF: 0.0638

GnomAD4 exome AF: 0.0671 AC: 97729 AN: 1456396 Hom.: 4453 Cov.: 31 AF XY: 0.0712 AC XY: 51552 AN XY: 723560

African (AFR) AF: 0.0264 AC: 881 AN: 33396

American (AMR) AF: 0.0243 AC: 1081 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.0367 AC: 956 AN: 26044

East Asian (EAS) AF: 0.134 AC: 5310 AN: 39530

South Asian (SAS) AF: 0.193 AC: 16539 AN: 85612

European-Finnish (FIN) AF: 0.0628 AC: 3345 AN: 53224

Middle Eastern (MID) AF: 0.0689 AC: 391 AN: 5676

European-Non Finnish (NFE) AF: 0.0588 AC: 65131 AN: 1108250

Other (OTH) AF: 0.0680 AC: 4095 AN: 60190

GnomAD4 genome AF: 0.0560 AC: 8529 AN: 152272 Hom.: 364 Cov.: 33 AF XY: 0.0592 AC XY: 4406 AN XY: 74464

African (AFR) AF: 0.0281 AC: 1166 AN: 41562

American (AMR) AF: 0.0346 AC: 530 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3470

East Asian (EAS) AF: 0.125 AC: 650 AN: 5182

South Asian (SAS) AF: 0.208 AC: 1000 AN: 4818

European-Finnish (FIN) AF: 0.0551 AC: 584 AN: 10600

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0618 AC: 4205 AN: 68018

Other (OTH) AF: 0.0487 AC: 103 AN: 2116

Alfa AF: 0.0608 Hom.: 1481

Bravo AF: 0.0493

TwinsUK AF: 0.0566 AC: 210

ALSPAC AF: 0.0592 AC: 228

ESP6500AA AF: 0.0291 AC: 128

ESP6500EA AF: 0.0571 AC: 491

ExAC AF: 0.0779 AC: 9455

Asia WGS AF: 0.154 AC: 536 AN: 3478

EpiCase AF: 0.0601

EpiControl AF: 0.0589

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PIWIL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.23	N
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.69	N
PhyloP100		4.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	0.97	T
Polyphen		0.0	B
Vest4		0.015
MPC		0.61
ClinPred		0.012	T
GERP RS		4.3
Varity_R		0.066
gMVP		0.34
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: rs1106042; hg19: chr12-130841638; COSMIC: COSV55346722;