Variant 5-168408624-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000265293.9(WWC1):c.838G>A(p.Val280Met) variant causes a missense change. The variant allele was found at a frequency of 0.000336 in 1,614,190 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 3 hom. )

Consequence

WWC1
ENST00000265293.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.67

Variant links:

Genes affected

WWC1 (HGNC:29435): (WW and C2 domain containing 1) The protein encoded by this gene is a cytoplasmic phosphoprotein that interacts with PRKC-zeta and dynein light chain-1. Alleles of this gene have been found that enhance memory in some individuals. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

WWC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006863922).

BP6

Variant 5-168408624-G-A is Benign according to our data. Variant chr5-168408624-G-A is described in ClinVar as [Benign]. Clinvar id is 732367.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC1	NM_015238.3 linkuse as main transcript	c.838G>A	p.Val280Met	missense_variant	7/23	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9 linkuse as main transcript	c.838G>A	p.Val280Met	missense_variant	7/23	1	NM_015238.3	ENSP00000265293	P1	Q8IX03-1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

284

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00661

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.00144

GnomAD3 exomes

AF:

0.000501

AC:

126

AN:

251338

Hom.:

AF XY:

0.000331

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00744

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000176

AC:

258

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

104

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00690

Gnomad4 AMR exome

AF:

0.000291

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.00186

AC:

284

AN:

152334

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00659

Gnomad4 AMR

AF:

0.000457

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:

0.00142

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.00203

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000593

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.031

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.028

D;D

Polyphen

0.0040

B;B

Vest4

0.17

MVP

0.15

MPC

0.30

ClinPred

0.073

GERP RS

2.4

Varity_R

0.043

gMVP

0.34

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