16-79211789-C-A

Position:

chr16-79211789-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000566780.6(WWOX):c.1238C>A(p.Ser413Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0183 in 1,614,074 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S413C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.014 ( 17 hom., cov: 33)

Exomes 𝑓: 0.019 ( 289 hom. )

Consequence

WWOX
ENST00000566780.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.66

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:):

MAF 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=0.003261149).

BP6

Variant 16-79211789-C-A is Benign according to our data. Variant chr16-79211789-C-A is described in ClinVar as [Benign]. Clinvar id is 241099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-79211789-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0137 (2088/152302) while in subpopulation NFE AF= 0.0215 (1462/68006). AF 95% confidence interval is 0.0206. There are 17 homozygotes in gnomad4. There are 977 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4 linkuse as main transcript	c.1238C>A	p.Ser413Tyr	missense_variant	9/9	ENST00000566780.6	NP_057457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6 linkuse as main transcript	c.1238C>A	p.Ser413Tyr	missense_variant	9/9	1	NM_016373.4	ENSP00000457230	P1	Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2087

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00350

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0128

AC:

3186

AN:

248544

Hom.:

AF XY:

0.0132

AC XY:

1786

AN XY:

135062

show subpopulations

Gnomad AFR exome

AF:

0.00267

Gnomad AMR exome

AF:

0.00696

Gnomad ASJ exome

AF:

0.0210

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00621

Gnomad FIN exome

AF:

0.00661

Gnomad NFE exome

AF:

0.0204

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0187

AC:

27391

AN:

1461772

Hom.:

289

Cov.:

AF XY:

0.0185

AC XY:

13443

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.00742

Gnomad4 ASJ exome

AF:

0.0205

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00632

Gnomad4 FIN exome

AF:

0.00781

Gnomad4 NFE exome

AF:

0.0219

Gnomad4 OTH exome

AF:

0.0175

GnomAD4 genome

AF:

0.0137

AC:

2088

AN:

152302

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

977

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00349

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0182

Hom.:

Bravo

AF:

0.0134

TwinsUK

AF:

0.0275

AC:

102

ALSPAC

AF:

0.0246

AC:

ESP6500AA

AF:

0.00255

AC:

ESP6500EA

AF:

0.0218

AC:

181

ExAC

AF:

0.0127

AC:

1535

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0195

EpiControl

AF:

0.0204

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 31, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	WWOX: BP4, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 14, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Autosomal recessive spinocerebellar ataxia 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.060

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.51

N;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.070

B;B

Vest4

0.32

ClinPred

0.020

GERP RS

5.7

Varity_R

0.24

gMVP

0.38

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