Variant chrX-10110010-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015691.5(WWC3):c.1336G>A(p.Ala446Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000351 in 1,197,059 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 6 hem., cov: 22)

Exomes 𝑓: 0.000025 ( 0 hom. 10 hem. )

Consequence

WWC3
NM_015691.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.49

Variant links:

Genes affected

WWC3 (HGNC:29237): (WWC family member 3) This gene encodes a member of the WWC family of proteins, which also includes the WWC1 (KIBRA) gene product and the WWC2 gene product. The protein encoded by this gene includes a C2 domain, which is known to mediate homodimerization in the related WWC1 gene product. [provided by RefSeq, Sep 2011]

WWC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC3	NM_015691.5 linkuse as main transcript	c.1336G>A	p.Ala446Thr	missense_variant	10/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC3	ENST00000380861.10 linkuse as main transcript	c.1336G>A	p.Ala446Thr	missense_variant	10/24	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

112270

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34420

show subpopulations

Gnomad AFR

AF:

0.000421

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000935

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:

0.000656

GnomAD3 exomes

AF:

0.0000548

AC:

AN:

164173

Hom.:

AF XY:

0.0000531

AC XY:

AN XY:

56545

show subpopulations

Gnomad AFR exome

AF:

0.000265

Gnomad AMR exome

AF:

0.000115

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:

0.0000417

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000249

AC:

AN:

1084789

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

353551

show subpopulations

Gnomad4 AFR exome

AF:

0.000536

Gnomad4 AMR exome

AF:

0.0000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000188

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000838

Gnomad4 OTH exome

AF:

0.0000660

GnomAD4 genome

AF:

0.000134

AC:

AN:

112270

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34420

show subpopulations

Gnomad4 AFR

AF:

0.000421

Gnomad4 AMR

AF:

0.0000935

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:

0.000656

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000666

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.964G>A (p.A322T) alteration is located in exon 9 (coding exon 8) of the WWC3 gene. This alteration results from a G to A substitution at nucleotide position 964, causing the alanine (A) at amino acid position 322 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.035

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.82

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.1

REVEL

Benign

0.18

Sift

Uncertain

0.017

Sift4G

Uncertain

0.030

Polyphen

1.0

Vest4

0.89

MutPred

0.13

Loss of MoRF binding (P = 0.1363);

MVP

0.31

MPC

1.0

ClinPred

0.17

GERP RS

4.7

Varity_R

0.26

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over