16-78958895-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016373.4(WWOX):​c.1057-252713T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,016 control chromosomes in the GnomAD database, including 22,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 22046 hom., cov: 32)

Consequence

WWOX
NM_016373.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113

Publications

2 publications found
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 Gene-Disease associations (from GenCC):
  • genetic developmental and epileptic encephalopathy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • autosomal recessive spinocerebellar ataxia 12
    Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
  • developmental and epileptic encephalopathy, 28
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • 46,XY partial gonadal dysgenesis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • undetermined early-onset epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WWOXNM_016373.4 linkc.1057-252713T>A intron_variant Intron 8 of 8 ENST00000566780.6 NP_057457.1 Q9NZC7-1A0A411HBC7
WWOXNM_001291997.2 linkc.718-252713T>A intron_variant Intron 7 of 7 NP_001278926.1 Q9NZC7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WWOXENST00000566780.6 linkc.1057-252713T>A intron_variant Intron 8 of 8 1 NM_016373.4 ENSP00000457230.1 Q9NZC7-1

Frequencies

GnomAD3 genomes
AF:
0.530
AC:
80521
AN:
151900
Hom.:
22040
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.453
Gnomad AMI
AF:
0.479
Gnomad AMR
AF:
0.610
Gnomad ASJ
AF:
0.680
Gnomad EAS
AF:
0.910
Gnomad SAS
AF:
0.650
Gnomad FIN
AF:
0.513
Gnomad MID
AF:
0.640
Gnomad NFE
AF:
0.516
Gnomad OTH
AF:
0.555
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.530
AC:
80567
AN:
152016
Hom.:
22046
Cov.:
32
AF XY:
0.536
AC XY:
39835
AN XY:
74304
show subpopulations
African (AFR)
AF:
0.453
AC:
18770
AN:
41448
American (AMR)
AF:
0.611
AC:
9333
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.680
AC:
2361
AN:
3470
East Asian (EAS)
AF:
0.909
AC:
4706
AN:
5176
South Asian (SAS)
AF:
0.650
AC:
3131
AN:
4814
European-Finnish (FIN)
AF:
0.513
AC:
5417
AN:
10556
Middle Eastern (MID)
AF:
0.644
AC:
188
AN:
292
European-Non Finnish (NFE)
AF:
0.516
AC:
35046
AN:
67960
Other (OTH)
AF:
0.560
AC:
1180
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1873
3747
5620
7494
9367
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
712
1424
2136
2848
3560
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.510
Hom.:
2483
Bravo
AF:
0.537
Asia WGS
AF:
0.749
AC:
2601
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.5
DANN
Benign
0.78
PhyloP100
-0.11
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12596756; hg19: chr16-78992792; API