5-168414559-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4 BP6_Moderate BP7 BS2

The NM_015238.3(WWC1):c.1153C>A(p.Arg385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000745 in 1,553,270 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (2 hom.)
• Consequence: WWC1 NM_015238.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.29

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 5-168414559-C-A is Benign according to our data. Variant chr5-168414559-C-A is described in ClinVar as [Benign]. Clinvar id is 790569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.29 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC1	NM_015238.3	c.1153C>A	p.Arg385=	synonymous_variant	9/23	ENST00000265293.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC1	ENST00000265293.9	c.1153C>A	p.Arg385=	synonymous_variant	9/23	1	NM_015238.3	P1

Frequencies

GnomAD3 genomes AF: 0.00382 AC: 582 AN: 152166 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000957 AC: 150 AN: 156788 Hom.: 0 AF XY: 0.000718 AC XY: 60 AN XY: 83572

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.000479

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000663

Gnomad OTH exome AF: 0.000679

GnomAD4 exome AF: 0.000408 AC: 572 AN: 1400986 Hom.: 2 Cov.: 30 AF XY: 0.000352 AC XY: 243 AN XY: 691200

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.000666

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000148

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome AF: 0.00384 AC: 585 AN: 152284 Hom.: 3 Cov.: 33 AF XY: 0.00389 AC XY: 290 AN XY: 74456

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.000718

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00209 Hom.: 2

Bravo AF: 0.00471

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 21, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
Cadd	Benign	11
Dann	Benign	0.74

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: rs200207821; hg19: chr5-167841564;