rs383362

Positions:

chr16-79211923-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000402655.6(WWOX):c.725G>T(p.Ser242Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,541,148 control chromosomes in the GnomAD database, including 221,337 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17163 hom., cov: 33)

Exomes 𝑓: 0.53 ( 204174 hom. )

Consequence

WWOX
ENST00000402655.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

WWOX (HGNC:12799): (WW domain containing oxidoreductase) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family. This gene spans the FRA16D common chromosomal fragile site and appears to function as a tumor suppressor gene. Expression of the encoded protein is able to induce apoptosis, while defects in this gene are associated with multiple types of cancer. Disruption of this gene is also associated with autosomal recessive spinocerebellar ataxia 12. Disruption of a similar gene in mouse results in impaired steroidogenesis, additionally suggesting a metabolic function for the protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

WWOX links:

MAF (HGNC:6776): (MAF bZIP transcription factor) The protein encoded by this gene is a DNA-binding, leucine zipper-containing transcription factor that acts as a homodimer or as a heterodimer. Depending on the binding site and binding partner, the encoded protein can be a transcriptional activator or repressor. This protein plays a role in the regulation of several cellular processes, including embryonic lens fiber cell development, increased T-cell susceptibility to apoptosis, and chondrocyte terminal differentiation. Defects in this gene are a cause of juvenile-onset pulverulent cataract as well as congenital cerulean cataract 4 (CCA4). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

MAF links:

WWOX (HGNC:):

WWOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7422438E-4).

BP6

Variant 16-79211923-G-T is Benign according to our data. Variant chr16-79211923-G-T is described in ClinVar as [Benign]. Clinvar id is 1247128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4 linkuse as main transcript	c.*127G>T		3_prime_UTR_variant	9/9	ENST00000566780.6	NP_057457.1	Q9NZC7-1A0A411HBC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6 linkuse as main transcript	c.*127G>T		3_prime_UTR_variant	9/9	1	NM_016373.4	ENSP00000457230.1		Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69715

AN:

151992

Hom.:

17157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.480

GnomAD3 exomes

AF:

0.436

AC:

64037

AN:

146858

Hom.:

15752

AF XY:

0.442

AC XY:

35058

AN XY:

79310

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.532

Gnomad EAS exome

AF:

0.128

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.569

Gnomad OTH exome

AF:

0.485

GnomAD4 exome

AF:

0.532

AC:

739425

AN:

1389038

Hom.:

204174

Cov.:

AF XY:

0.529

AC XY:

362518

AN XY:

685916

show subpopulations

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.534

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.365

Gnomad4 FIN exome

AF:

0.540

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.495

GnomAD4 genome

AF:

0.459

AC:

69747

AN:

152110

Hom.:

17163

Cov.:

AF XY:

0.450

AC XY:

33467

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.358

Gnomad4 ASJ

AF:

0.536

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.545

Gnomad4 NFE

AF:

0.563

Gnomad4 OTH

AF:

0.474

Alfa

AF:

0.530

Hom.:

49056

Bravo

AF:

0.442

TwinsUK

AF:

0.567

AC:

2103

ALSPAC

AF:

0.574

AC:

2214

ExAC

AF:

0.366

AC:

33799

Asia WGS

AF:

0.242

AC:

842

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 54% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 50. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.5

DANN

Benign

0.78

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.19

MetaRNN

Benign

0.00017

MetaSVM

Benign

-0.92

PROVEAN

Benign

-0.14

REVEL

Benign

0.092

Sift

Benign

0.44

Sift4G

Benign

0.67

Polyphen

0.92

Vest4

0.20

ClinPred

0.020

GERP RS

1.4

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over