Variant chr22-24748945-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001255975.1(PIWIL3):c.1411G>A(p.Val471Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,611,530 control chromosomes in the GnomAD database, including 39,472 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.20 ( 3509 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35963 hom. )

Consequence

PIWIL3
NM_001255975.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00345546).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIWIL3	NM_001255975.1 linkuse as main transcript	c.1411G>A	p.Val471Ile	missense_variant	12/21	ENST00000616349.5	NP_001242904.1	A0A8J9G8U8B4DYF7
PIWIL3	NM_001008496.3 linkuse as main transcript	c.1411G>A	p.Val471Ile	missense_variant	12/21		NP_001008496.2	Q7Z3Z3
PIWIL3	NR_045648.1 linkuse as main transcript	n.2042G>A		non_coding_transcript_exon_variant	13/22
PIWIL3	NR_045649.2 linkuse as main transcript	n.1915G>A		non_coding_transcript_exon_variant	13/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIWIL3	ENST00000616349.5 linkuse as main transcript	c.1411G>A	p.Val471Ile	missense_variant	12/21	1	NM_001255975.1	ENSP00000479524.2		A0A8J9G8U8

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31118

AN:

151988

Hom.:

3510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.232

AC:

58157

AN:

250202

Hom.:

7857

AF XY:

0.225

AC XY:

30445

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.434

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.216

AC:

315482

AN:

1459424

Hom.:

35963

Cov.:

AF XY:

0.214

AC XY:

155645

AN XY:

726006

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.420

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.205

AC:

31130

AN:

152106

Hom.:

3509

Cov.:

AF XY:

0.206

AC XY:

15317

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.216

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.208

Hom.:

8410

Bravo

AF:

0.214

TwinsUK

AF:

0.225

AC:

834

ALSPAC

AF:

0.221

AC:

851

ESP6500AA

AF:

0.147

AC:

648

ESP6500EA

AF:

0.214

AC:

1837

ExAC

AF:

0.224

AC:

27226

Asia WGS

AF:

0.164

AC:

570

AN:

3478

EpiCase

AF:

0.210

EpiControl

AF:

0.210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.21

DANN

Benign

0.61

DEOGEN2

Benign

0.0050

T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.41

T;.;.;T

MetaRNN

Benign

0.0035

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

L;L;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.33

.;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.47

.;T;T;T

Sift4G

Benign

0.39

T;T;T;T

Polyphen

0.10

B;B;B;B

Vest4

0.024

MPC

0.088

ClinPred

0.00042

GERP RS

-3.9

Varity_R

0.021

gMVP

0.049

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over