rs79771882

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_016373.4(WWOX):​c.885G>A​(p.Arg295=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00891 in 1,614,140 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0090 ( 13 hom., cov: 32)
Exomes 𝑓: 0.0089 ( 101 hom. )

Consequence

WWOX
NM_016373.4 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.0280
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 16-78432581-G-A is Benign according to our data. Variant chr16-78432581-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212617.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=3}.
BP7
Synonymous conserved (PhyloP=-0.028 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00899 (1368/152252) while in subpopulation NFE AF= 0.00806 (548/68030). AF 95% confidence interval is 0.0075. There are 13 homozygotes in gnomad4. There are 757 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WWOXNM_016373.4 linkuse as main transcriptc.885G>A p.Arg295= synonymous_variant 8/9 ENST00000566780.6
WWOXNM_001291997.2 linkuse as main transcriptc.546G>A p.Arg182= synonymous_variant 7/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WWOXENST00000566780.6 linkuse as main transcriptc.885G>A p.Arg295= synonymous_variant 8/91 NM_016373.4 P1Q9NZC7-1

Frequencies

GnomAD3 genomes
AF:
0.00900
AC:
1369
AN:
152132
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00606
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00544
Gnomad ASJ
AF:
0.00404
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00270
Gnomad FIN
AF:
0.0416
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00805
Gnomad OTH
AF:
0.00909
GnomAD3 exomes
AF:
0.00857
AC:
2139
AN:
249566
Hom.:
32
AF XY:
0.00840
AC XY:
1137
AN XY:
135400
show subpopulations
Gnomad AFR exome
AF:
0.00646
Gnomad AMR exome
AF:
0.00446
Gnomad ASJ exome
AF:
0.00288
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00186
Gnomad FIN exome
AF:
0.0398
Gnomad NFE exome
AF:
0.00779
Gnomad OTH exome
AF:
0.00957
GnomAD4 exome
AF:
0.00890
AC:
13013
AN:
1461888
Hom.:
101
Cov.:
32
AF XY:
0.00862
AC XY:
6269
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00741
Gnomad4 AMR exome
AF:
0.00434
Gnomad4 ASJ exome
AF:
0.00279
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00179
Gnomad4 FIN exome
AF:
0.0370
Gnomad4 NFE exome
AF:
0.00890
Gnomad4 OTH exome
AF:
0.00758
GnomAD4 genome
AF:
0.00899
AC:
1368
AN:
152252
Hom.:
13
Cov.:
32
AF XY:
0.0102
AC XY:
757
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.00604
Gnomad4 AMR
AF:
0.00543
Gnomad4 ASJ
AF:
0.00404
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00270
Gnomad4 FIN
AF:
0.0416
Gnomad4 NFE
AF:
0.00806
Gnomad4 OTH
AF:
0.00852
Alfa
AF:
0.00812
Hom.:
4
Bravo
AF:
0.00641
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.00796
EpiControl
AF:
0.00812

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJun 27, 2014- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 01, 2016This 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. -
not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2024WWOX: BP4, BP7, BS2 -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsApr 25, 2018- -
Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 30, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
4.2
DANN
Benign
0.68

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.

Other links and lift over

dbSNP: rs79771882; hg19: chr16-78466478; API