16-79211690-G-C

Position:

• chr16-79211690-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000566780.6(WWOX):​c.1139G>C​(p.Cys380Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 10/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C380Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WWOX ENST00000566780.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63

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]

MAF (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1139G>C	p.Cys380Ser	missense_variant	9/9	ENST00000566780.6	NP_057457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1139G>C	p.Cys380Ser	missense_variant	9/9	1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 89

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.99	D;D;N;N
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.23	T
Vest4		0.57
MutPred		0.26		Loss of sheet (P = 0.0181);
MVP		0.78
ClinPred		0.92	D
GERP RS		3.7

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

Other links and lift over

dbSNP: rs758746365; hg19: chr16-79245587;