Variant 5-168408534-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015238.3(WWC1):c.748C>T(p.Arg250Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,613,978 control chromosomes in the GnomAD database, including 18,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1187 hom., cov: 31)

Exomes 𝑓: 0.15 ( 16959 hom. )

Consequence

WWC1
NM_015238.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.34

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019046664).

BP6

Variant 5-168408534-C-T is Benign according to our data. Variant chr5-168408534-C-T is described in ClinVar as [Benign]. Clinvar id is 1245599.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC1	NM_015238.3 linkuse as main transcript	c.748C>T	p.Arg250Cys	missense_variant	7/23	ENST00000265293.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC1	ENST00000265293.9 linkuse as main transcript	c.748C>T	p.Arg250Cys	missense_variant	7/23	1	NM_015238.3	P1	Q8IX03-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17312

AN:

152088

Hom.:

1187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0433

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.00462

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.122

AC:

30545

AN:

251194

Hom.:

2197

AF XY:

0.126

AC XY:

17109

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.0415

Gnomad AMR exome

AF:

0.0801

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.00435

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.147

AC:

214333

AN:

1461772

Hom.:

16959

Cov.:

AF XY:

0.146

AC XY:

106332

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0384

Gnomad4 AMR exome

AF:

0.0831

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.00378

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.139

GnomAD4 genome

AF:

0.114

AC:

17312

AN:

152206

Hom.:

1187

Cov.:

AF XY:

0.113

AC XY:

8408

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.00463

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.143

Hom.:

4334

Bravo

AF:

0.104

TwinsUK

AF:

0.170

AC:

629

ALSPAC

AF:

0.160

AC:

617

ESP6500AA

AF:

0.0443

AC:

195

ESP6500EA

AF:

0.156

AC:

1339

ExAC

AF:

0.121

AC:

14713

Asia WGS

AF:

0.0550

AC:

192

AN:

3478

EpiCase

AF:

0.163

EpiControl

AF:

0.155

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

GeneDx

Nov 02, 2020

This variant is associated with the following publications: (PMID: 26405221) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.038

Eigen_PC

Benign

-0.034

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.0063

P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.017

D;D

Sift4G

Benign

0.099

T;T

Polyphen

0.94

P;P

Vest4

0.083

MPC

0.38

ClinPred

0.013

GERP RS

4.3

Varity_R

0.088

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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