5-168292238-A-G

Position:

• chr5-168292238-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015238.3(WWC1):​c.86A>G​(p.Asn29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: WWC1 NM_015238.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.128

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]

WWC1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037514).
• BP6: Variant 5-168292238-A-G is Benign according to our data. Variant chr5-168292238-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2534742.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC1	NM_015238.3	c.86A>G	p.Asn29Ser	missense_variant	1/23	ENST00000265293.9	NP_056053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9	c.86A>G	p.Asn29Ser	missense_variant	1/23	1	NM_015238.3	ENSP00000265293.4
WWC1	ENST00000521089.5	c.86A>G	p.Asn29Ser	missense_variant	1/23	2		ENSP00000427772.1
WWC1	ENST00000523043.5	n.-8A>G		upstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.16	N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.12	N;N
REVEL	Benign	0.095
Sift	Benign	0.99	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0	B;B
Vest4		0.028
MutPred		0.42		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.40
MPC		0.23
ClinPred		0.092	T
GERP RS		-0.36
Varity_R		0.028
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-167719243;