rs10521608

Positions:

• chrX-10075291-C-A
• chrX-10075291-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015691.5(WWC3):​c.593-3508C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 112,307 control chromosomes in the GnomAD database, including 39 homozygotes. There are 668 hemizygotes in GnomAD. 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 0.017 (39 hom., 668 hem., cov: 23)
• Consequence: WWC3 NM_015691.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

Genes affected

WWC3 (HGNC:29237): (WWC family member 3) This gene encodes a member of the WWC family of proteins, which also includes the WWC1 (KIBRA) gene product and the WWC2 gene product. The protein encoded by this gene includes a C2 domain, which is known to mediate homodimerization in the related WWC1 gene product. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC3	NM_015691.5	c.593-3508C>A		intron_variant			NP_056506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC3	ENST00000380861.10	c.593-3508C>A		intron_variant		1		ENSP00000370242	P1

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 1873 AN: 112250 Hom.: 40 Cov.: 23 AF XY: 0.0194 AC XY: 667 AN XY: 34430

Gnomad AFR AF: 0.00443

Gnomad AMI AF: 0.0102

Gnomad AMR AF: 0.00819

Gnomad ASJ AF: 0.00867

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0167 AC: 1875 AN: 112307 Hom.: 39 Cov.: 23 AF XY: 0.0194 AC XY: 668 AN XY: 34497

Gnomad4 AFR AF: 0.00442

Gnomad4 AMR AF: 0.00837

Gnomad4 ASJ AF: 0.00867

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0104 Hom.: 45

Bravo AF: 0.0148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	11
DANN	Benign	0.77

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: rs10521608; hg19: chrX-10043331;