rs79771882
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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
NM_016373.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0280
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]
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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 |
---|---|---|---|---|---|---|---|
WWOX | NM_016373.4 | c.885G>A | p.Arg295= | synonymous_variant | 8/9 | ENST00000566780.6 | |
WWOX | NM_001291997.2 | c.546G>A | p.Arg182= | synonymous_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WWOX | ENST00000566780.6 | c.885G>A | p.Arg295= | synonymous_variant | 8/9 | 1 | NM_016373.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00900 AC: 1369AN: 152132Hom.: 13 Cov.: 32
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GnomAD3 exomes AF: 0.00857 AC: 2139AN: 249566Hom.: 32 AF XY: 0.00840 AC XY: 1137AN XY: 135400
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GnomAD4 exome AF: 0.00890 AC: 13013AN: 1461888Hom.: 101 Cov.: 32 AF XY: 0.00862 AC XY: 6269AN XY: 727246
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GnomAD4 genome AF: 0.00899 AC: 1368AN: 152252Hom.: 13 Cov.: 32 AF XY: 0.0102 AC XY: 757AN XY: 74422
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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 submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 27, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 01, 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. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | WWOX: BP4, BP7, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 25, 2018 | - - |
Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at