rs3822660

Variant names:

• chr5-168431366-G-T
• rs3822660
• NM_015238.3:c.2202G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015238.3(WWC1):​c.2202G>T​(p.Met734Ile) 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 1,613,366 control chromosomes in the GnomAD database, including 6,997 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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 (1772 hom., cov: 32)
  • Exomes 𝑓: 0.074 (5225 hom.)
• Consequence: WWC1 NM_015238.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 21 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018526018).
• 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	c.2202G>T	p.Met734Ile	missense_variant	Exon 15 of 23	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.2202G>T	p.Met734Ile	missense_variant	Exon 15 of 23	1	NM_015238.3	ENSP00000265293.4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18734 AN: 151854 Hom.: 1770 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0624

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.0870 AC: 21855 AN: 251064 AF XY: 0.0840

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.0463

Gnomad ASJ exome AF: 0.0930

Gnomad EAS exome AF: 0.244

Gnomad FIN exome AF: 0.0465

Gnomad NFE exome AF: 0.0607

Gnomad OTH exome AF: 0.0853

GnomAD4 exome AF: 0.0736 AC: 107561 AN: 1461394 Hom.: 5225 Cov.: 30 AF XY: 0.0730 AC XY: 53098 AN XY: 727014

African (AFR) AF: 0.269 AC: 8998 AN: 33430

American (AMR) AF: 0.0503 AC: 2250 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 2296 AN: 26118

East Asian (EAS) AF: 0.185 AC: 7349 AN: 39668

South Asian (SAS) AF: 0.0709 AC: 6107 AN: 86190

European-Finnish (FIN) AF: 0.0460 AC: 2454 AN: 53388

Middle Eastern (MID) AF: 0.119 AC: 684 AN: 5764

European-Non Finnish (NFE) AF: 0.0647 AC: 71906 AN: 1111776

Other (OTH) AF: 0.0914 AC: 5517 AN: 60366

GnomAD4 genome AF: 0.123 AC: 18754 AN: 151972 Hom.: 1772 Cov.: 32 AF XY: 0.121 AC XY: 9012 AN XY: 74306

African (AFR) AF: 0.262 AC: 10826 AN: 41376

American (AMR) AF: 0.0670 AC: 1024 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1132 AN: 5132

South Asian (SAS) AF: 0.0809 AC: 390 AN: 4822

European-Finnish (FIN) AF: 0.0477 AC: 506 AN: 10606

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0623 AC: 4237 AN: 67968

Other (OTH) AF: 0.107 AC: 225 AN: 2110

Alfa AF: 0.0887 Hom.: 2056

Bravo AF: 0.134

ExAC AF: 0.0908 AC: 11021

Asia WGS AF: 0.165 AC: 572 AN: 3474

EpiCase AF: 0.0676

EpiControl AF: 0.0686

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.023	T;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.82	T;T;T
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.4	N;N;.
PhyloP100		-0.038
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.3	N;N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.81	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.16
MutPred		0.23		Gain of catalytic residue at L739 (P = 0.142);Gain of catalytic residue at L739 (P = 0.142);.;
MPC		0.31
ClinPred		0.0031	T
GERP RS		1.2
Varity_R		0.098
gMVP		0.19
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3822660; hg19: chr5-167858371; COSMIC: COSV54646489;