16-78099740-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_016373.4(WWOX):c.-39A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000758 in 1,517,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 1 hom. )

Consequence

WWOX
NM_016373.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.849

Publications

0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
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

WWOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 16-78099740-A-T is Benign according to our data. Variant chr16-78099740-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 514318.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000388 (59/152236) while in subpopulation AFR AF = 0.00128 (53/41468). AF 95% confidence interval is 0.001. There are 0 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WWOX	NM_016373.4	MANE Select	c.-39A>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_057457.1	Q9NZC7-1
WWOX	NM_016373.4	MANE Select	c.-39A>T	5_prime_UTR	Exon 1 of 9	NP_057457.1	Q9NZC7-1
WWOX	NM_001291997.2		c.-313A>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001278926.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WWOX	ENST00000566780.6	TSL:1 MANE Select	c.-39A>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000457230.1	Q9NZC7-1
WWOX	ENST00000408984.7	TSL:1	c.-39A>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000386161.3	Q9NZC7-2
WWOX	ENST00000402655.6	TSL:1	c.-39A>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000384238.2	Q9NZC7-6

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000117

AC:

AN:

120100

AF XY:

0.0000923

show subpopulations

Gnomad AFR exome

AF:

0.00238

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000306

GnomAD4 exome

AF:

0.0000410

AC:

AN:

1364820

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

671904

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

29294

American (AMR)

AF:

0.0000675

AC:

AN:

29642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23490

East Asian (EAS)

AF:

0.00

AC:

AN:

33790

South Asian (SAS)

AF:

0.0000133

AC:

AN:

75270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47848

Middle Eastern (MID)

AF:

0.000239

AC:

AN:

4186

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064910

Other (OTH)

AF:

0.000106

AC:

AN:

56390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000388

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

41468

American (AMR)

AF:

0.000262

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000434

Hom.:

Bravo

AF:

0.000355

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

3.6

(source)

DANN

Benign

0.58

PhyloP100

-0.85

PromoterAI

-0.0054

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over