chrX-10054097-G-A

Position:

• chrX-10054097-G-A

Variant summary

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

The ENST00000380861.10(WWC3):​c.279-9348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 110,222 control chromosomes in the GnomAD database, including 3,037 homozygotes. There are 4,633 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 0.16 (3037 hom., 4633 hem., cov: 22)
• Consequence: WWC3 ENST00000380861.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC3	NM_015691.5	c.279-9348G>A		intron_variant			NP_056506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC3	ENST00000380861.10	c.279-9348G>A		intron_variant		1		ENSP00000370242	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 17596 AN: 110173 Hom.: 3036 Cov.: 22 AF XY: 0.142 AC XY: 4602 AN XY: 32499

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0178

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.160 AC: 17635 AN: 110222 Hom.: 3037 Cov.: 22 AF XY: 0.142 AC XY: 4633 AN XY: 32558

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.0178

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0101

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.141

Alfa AF: 0.116 Hom.: 1500

Bravo AF: 0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.75
DANN	Benign	0.59

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: rs7880027; hg19: chrX-10022137;