Genetic Variant NM_015238.3:c.2203T>G (chr5-168431367-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015238.3(WWC1):c.2203T>G(p.Ser735Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 1,613,386 control chromosomes in the GnomAD database, including 6,998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1773 hom., cov: 32)

Exomes 𝑓: 0.074 ( 5225 hom. )

Consequence

WWC1
NM_015238.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.56

Publications

24 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017426908).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3 link	c.2203T>G	p.Ser735Ala	missense_variant	Exon 15 of 23	ENST00000265293.9	NP_056053.1	Q8IX03-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9 link	c.2203T>G	p.Ser735Ala	missense_variant	Exon 15 of 23	1	NM_015238.3	ENSP00000265293.4		Q8IX03-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18738

AN:

151872

Hom.:

1771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0673

Gnomad ASJ

AF:

0.0839

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.0809

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0623

Gnomad OTH

AF:

0.106

GnomAD2 exomes

AF:

0.0870

AC:

21854

AN:

251070

AF XY:

0.0840

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.0464

Gnomad ASJ exome

AF:

0.0929

Gnomad EAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.0464

Gnomad NFE exome

AF:

0.0607

Gnomad OTH exome

AF:

0.0851

GnomAD4 exome

AF:

0.0736

AC:

107564

AN:

1461396

Hom.:

5225

Cov.:

AF XY:

0.0730

AC XY:

53099

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.269

AC:

8998

AN:

33430

American (AMR)

AF:

0.0504

AC:

2255

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0879

AC:

2295

AN:

26116

East Asian (EAS)

AF:

0.185

AC:

7350

AN:

39666

South Asian (SAS)

AF:

0.0709

AC:

6110

AN:

86198

European-Finnish (FIN)

AF:

0.0459

AC:

2451

AN:

53384

Middle Eastern (MID)

AF:

0.119

AC:

684

AN:

5764

European-Non Finnish (NFE)

AF:

0.0647

AC:

71905

AN:

1111770

Other (OTH)

AF:

0.0914

AC:

5516

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

5187

10374

15562

20749

25936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2932

5864

8796

11728

14660

<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:

0.123

AC:

18758

AN:

151990

Hom.:

1773

Cov.:

AF XY:

0.121

AC XY:

9012

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.262

AC:

10829

AN:

41386

American (AMR)

AF:

0.0671

AC:

1025

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0839

AC:

291

AN:

3470

East Asian (EAS)

AF:

0.220

AC:

1132

AN:

5138

South Asian (SAS)

AF:

0.0809

AC:

390

AN:

4818

European-Finnish (FIN)

AF:

0.0477

AC:

506

AN:

10602

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0623

AC:

4237

AN:

67988

Other (OTH)

AF:

0.107

AC:

225

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

769

1538

2306

3075

3844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0864

Hom.:

3243

Bravo

AF:

0.134

ExAC

AF:

0.0908

AC:

11021

Asia WGS

AF:

0.165

AC:

572

AN:

3474

EpiCase

AF:

0.0677

EpiControl

AF:

0.0687

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.031

T;.;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M;.

PhyloP100

3.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.091

Sift

Benign

0.16

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.077

B;B;.

Vest4

0.59

MPC

0.56

ClinPred

0.033

GERP RS

5.2

Varity_R

0.30

gMVP

0.23

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over