dbSNP rs11703684: PIWIL3:p.Val471Leu (chr22-24748945-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001255975.1(PIWIL3):c.1411G>C(p.Val471Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

PIWIL3
NM_001255975.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

30 publications found

Variant links:

Genes affected

PIWIL3 (HGNC:18443): (piwi like RNA-mediated gene silencing 3) This gene encodes a member of the PIWI subfamily of Argonaute family proteins. This subfamily of proteins contains a PAZ domain, found in proteins involved in RNA-mediated gene silencing, and a C-terminal Piwi domain. The encoded protein is thought to function in maintenance of germline cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

PIWIL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065521896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PIWIL3	NM_001255975.1 link	c.1411G>C	p.Val471Leu	missense_variant	Exon 12 of 21	ENST00000616349.5	NP_001242904.1
PIWIL3	NM_001008496.3 link	c.1411G>C	p.Val471Leu	missense_variant	Exon 12 of 21		NP_001008496.2
PIWIL3	NR_045648.1 link	n.2042G>C		non_coding_transcript_exon_variant	Exon 13 of 22
PIWIL3	NR_045649.2 link	n.1915G>C		non_coding_transcript_exon_variant	Exon 13 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIWIL3	ENST00000616349.5 link	c.1411G>C	p.Val471Leu	missense_variant	Exon 12 of 21	1	NM_001255975.1	ENSP00000479524.2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

11590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.7

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0091

T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.43

T;.;.;T

M_CAP

Benign

0.00064

MetaRNN

Benign

0.066

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;.;.

PhyloP100

-0.064

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

.;N;N;N

REVEL

Benign

0.012

Sift

Benign

0.068

.;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.026

B;B;B;B

Vest4

0.090

MutPred

0.38

Loss of methylation at K473 (P = 0.0778);Loss of methylation at K473 (P = 0.0778);.;.;

MVP

0.072

MPC

0.11

ClinPred

0.12

GERP RS

-3.9

Varity_R

0.066

gMVP

0.10

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over