Variant 22-24719498-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001255975.1(PIWIL3):c.2596T>G(p.Leu866Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,444,022 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PIWIL3
NM_001255975.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55

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:

PIWIL3 (HGNC:):

PIWIL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIWIL3	NM_001255975.1 linkuse as main transcript	c.2596T>G	p.Leu866Val	missense_variant	21/21	ENST00000616349.5	NP_001242904.1	A0A8J9G8U8B4DYF7
PIWIL3	NM_001008496.3 linkuse as main transcript	c.2623T>G	p.Leu875Val	missense_variant	21/21		NP_001008496.2	Q7Z3Z3
PIWIL3	NR_045648.1 linkuse as main transcript	n.3227T>G		non_coding_transcript_exon_variant	22/22
PIWIL3	NR_045649.2 linkuse as main transcript	n.3100T>G		non_coding_transcript_exon_variant	22/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIWIL3	ENST00000616349.5 linkuse as main transcript	c.2596T>G	p.Leu866Val	missense_variant	21/21	1	NM_001255975.1	ENSP00000479524.2		A0A8J9G8U8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1444022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717470

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.2623T>G (p.L875V) alteration is located in exon 21 (coding exon 20) of the PIWIL3 gene. This alteration results from a T to G substitution at nucleotide position 2623, causing the leucine (L) at amino acid position 875 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;T;.;.

Eigen

Benign

0.032

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.89

D;.;.;D

M_CAP

Benign

0.0032

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

4.0

H;H;.;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.4

.;N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0020

.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.35

MutPred

0.76

Gain of MoRF binding (P = 0.1507);Gain of MoRF binding (P = 0.1507);.;.;

MVP

0.36

MPC

0.54

ClinPred

0.97

GERP RS

-0.56

Varity_R

0.26

gMVP

0.29

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over