5-168292259-A-G

Position:

• chr5-168292259-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015238.3(WWC1):​c.107A>G​(p.Asp36Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WWC1 NM_015238.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.74

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC1	NM_015238.3	c.107A>G	p.Asp36Gly	missense_variant	1/23	ENST00000265293.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC1	ENST00000265293.9	c.107A>G	p.Asp36Gly	missense_variant	1/23	1	NM_015238.3	P1
WWC1	ENST00000521089.5	c.107A>G	p.Asp36Gly	missense_variant	1/23	2
WWC1	ENST00000523043.5	n.14A>G		non_coding_transcript_exon_variant	1/6	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446584 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718272

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.107A>G (p.D36G) alteration is located in exon 1 (coding exon 1) of the WWC1 gene. This alteration results from a A to G substitution at nucleotide position 107, causing the aspartic acid (D) at amino acid position 36 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;.
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.91	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Pathogenic	3.4	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-4.0	D;D
REVEL	Pathogenic	0.88
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.94	P;B
Vest4		0.80
MutPred		0.69		Loss of stability (P = 0.027);Loss of stability (P = 0.027);
MVP		0.81
MPC		0.66
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.58
gMVP		0.72

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: chr5-167719264;