rs3822659

Positions:

• chr5-168431367-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1773 hom., cov: 32)
  • Exomes 𝑓: 0.074 (5225 hom.)
• Consequence: WWC1 NM_015238.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
WWC1	NM_015238.3	c.2203T>G	p.Ser735Ala	missense_variant	15/23	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.2203T>G	p.Ser735Ala	missense_variant	15/23	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18738 AN: 151872 Hom.: 1771 Cov.: 32

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

GnomAD3 exomes AF: 0.0870 AC: 21854 AN: 251070 Hom.: 1596 AF XY: 0.0840 AC XY: 11395 AN XY: 135734

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 SAS exome AF: 0.0708

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.: 30 AF XY: 0.0730 AC XY: 53099 AN XY: 727018

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.0879

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.0709

Gnomad4 FIN exome AF: 0.0459

Gnomad4 NFE exome AF: 0.0647

Gnomad4 OTH exome AF: 0.0914

GnomAD4 genome AF: 0.123 AC: 18758 AN: 151990 Hom.: 1773 Cov.: 32 AF XY: 0.121 AC XY: 9012 AN XY: 74310

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.0809

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0773 Hom.: 1558

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	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.031	T;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.69	T;T;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;M;.
PrimateAI	Uncertain	0.51	T
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	T
GERP RS		5.2
Varity_R		0.30
gMVP		0.23

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: rs3822659; hg19: chr5-167858372; COSMIC: COSV54646512;