16-78099774-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_016373.4(WWOX):c.-5C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,541,828 control chromosomes in the GnomAD database, including 80,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6339 hom., cov: 33)

Exomes 𝑓: 0.32 ( 74319 hom. )

Consequence

WWOX
NM_016373.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.258

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 16-78099774-C-T is Benign according to our data. Variant chr16-78099774-C-T is described in ClinVar as [Benign]. Clinvar id is 260735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWOX	NM_016373.4 link	c.-5C>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000566780.6	NP_057457.1	Q9NZC7-1A0A411HBC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780 link	c.-5C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_016373.4	ENSP00000457230.1		Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42307

AN:

152068

Hom.:

6335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.300

AC:

44471

AN:

148386

Hom.:

6949

AF XY:

0.301

AC XY:

24052

AN XY:

79884

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

AF:

0.324

AC:

449999

AN:

1389642

Hom.:

74319

Cov.:

AF XY:

0.322

AC XY:

220932

AN XY:

685744

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.352

Gnomad4 NFE exome

AF:

0.338

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.278

AC:

42315

AN:

152186

Hom.:

6339

Cov.:

AF XY:

0.277

AC XY:

20642

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.269

Alfa

AF:

0.322

Hom.:

11546

Bravo

AF:

0.268

Asia WGS

AF:

0.191

AC:

665

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 06, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 43. Only high quality variants are reported. -

not provided

Benign:2

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 28

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive spinocerebellar ataxia 12

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over