5-168431457-TCTGGCTGGCTGGCTGGCTGGCTGGCTGG-TCTGGCTGGCTGGCTGGCTGGCTGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015238.3(WWC1):c.2280+57_2280+60del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,406,984 control chromosomes in the GnomAD database, including 105,519 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11745 hom., cov: 0)
  • Exomes 𝑓: 0.39 (93774 hom.)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-168431457-TCTGG-T is Benign according to our data. Variant chr5-168431457-TCTGG-T is described in ClinVar as [Benign]. Clinvar id is 403611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC1	NM_015238.3	c.2280+57_2280+60del		intron_variant		ENST00000265293.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC1	ENST00000265293.9	c.2280+57_2280+60del		intron_variant		1	NM_015238.3	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 56792 AN: 148060 Hom.: 11741 Cov.: 0

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.428

GnomAD3 exomes AF: 0.349 AC: 44091 AN: 126504 Hom.: 8000 AF XY: 0.357 AC XY: 24246 AN XY: 68006

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.186

Gnomad SAS exome AF: 0.370

Gnomad FIN exome AF: 0.376

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.388 AC: 488354 AN: 1258818 Hom.: 93774 AF XY: 0.390 AC XY: 243934 AN XY: 624868

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.383 AC: 56818 AN: 148166 Hom.: 11745 Cov.: 0 AF XY: 0.381 AC XY: 27476 AN XY: 72038

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.429

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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: rs11279828; hg19: chr5-167858462;