rs373306276
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016373.4(WWOX):c.321C>A(p.Tyr107*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
WWOX
NM_016373.4 stop_gained
NM_016373.4 stop_gained
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: -0.338
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 Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-78115066-C-A is Pathogenic according to our data. Variant chr16-78115066-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1180630.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| WWOX | NM_016373.4 | c.321C>A | p.Tyr107* | stop_gained | Exon 4 of 9 | ENST00000566780.6 | NP_057457.1 | |
| WWOX | NM_130791.5 | c.321C>A | p.Tyr107* | stop_gained | Exon 4 of 6 | NP_570607.1 | ||
| WWOX | NM_001291997.2 | c.-19C>A | 5_prime_UTR_variant | Exon 3 of 8 | NP_001278926.1 | |||
| WWOX | NR_120436.3 | n.560C>A | non_coding_transcript_exon_variant | Exon 4 of 6 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461880Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727238
GnomAD4 exome
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3
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1461880
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34
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1
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727238
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
Bravo
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Abnormality of the nervous system Pathogenic:1
Jul 10, 2021
Kariminejad - Najmabadi Pathology & Genetics Center
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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