rs376279847

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_016373.4(WWOX):​c.618G>A​(p.Val206Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

WWOX
NM_016373.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.910
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 16-78424882-G-A is Benign according to our data. Variant chr16-78424882-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 387105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.91 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000723 (110/152078) while in subpopulation AFR AF= 0.00249 (103/41416). AF 95% confidence interval is 0.0021. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WWOXNM_016373.4 linkuse as main transcriptc.618G>A p.Val206Val synonymous_variant 7/9 ENST00000566780.6 NP_057457.1 Q9NZC7-1A0A411HBC7
WWOXNM_001291997.2 linkuse as main transcriptc.279G>A p.Val93Val synonymous_variant 6/8 NP_001278926.1 Q9NZC7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WWOXENST00000566780.6 linkuse as main transcriptc.618G>A p.Val206Val synonymous_variant 7/91 NM_016373.4 ENSP00000457230.1 Q9NZC7-1

Frequencies

GnomAD3 genomes
AF:
0.000723
AC:
110
AN:
152078
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00249
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000168
AC:
42
AN:
249548
Hom.:
0
AF XY:
0.000148
AC XY:
20
AN XY:
135386
show subpopulations
Gnomad AFR exome
AF:
0.00245
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000499
AC:
73
AN:
1461864
Hom.:
0
Cov.:
32
AF XY:
0.0000385
AC XY:
28
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00197
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000723
AC:
110
AN:
152078
Hom.:
0
Cov.:
32
AF XY:
0.000660
AC XY:
49
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.00249
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000957
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.000771

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 19, 2024- -
Developmental and epileptic encephalopathy, 28 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabDec 05, 2021- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 09, 2021- -
Autosomal recessive spinocerebellar ataxia 12 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabDec 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
1.0
DANN
Benign
0.42

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: rs376279847; hg19: chr16-78458779; API