chr5-168292172-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015238.3(WWC1):ā€‹c.20C>Gā€‹(p.Pro7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000042 in 1,546,358 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000044 ( 0 hom. )

Consequence

WWC1
NM_015238.3 missense

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WWC1NM_015238.3 linkuse as main transcriptc.20C>G p.Pro7Arg missense_variant 1/23 ENST00000265293.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WWC1ENST00000265293.9 linkuse as main transcriptc.20C>G p.Pro7Arg missense_variant 1/231 NM_015238.3 P1Q8IX03-1
WWC1ENST00000521089.5 linkuse as main transcriptc.20C>G p.Pro7Arg missense_variant 1/232 Q8IX03-2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151906
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000135
AC:
2
AN:
148566
Hom.:
0
AF XY:
0.0000126
AC XY:
1
AN XY:
79394
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000353
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000445
AC:
62
AN:
1394452
Hom.:
0
Cov.:
31
AF XY:
0.0000392
AC XY:
27
AN XY:
687906
show subpopulations
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:
0.0000529
Gnomad4 OTH exome
AF:
0.0000864
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
151906
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74182
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000180
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 06, 2022The c.20C>G (p.P7R) alteration is located in exon 1 (coding exon 1) of the WWC1 gene. This alteration results from a C to G substitution at nucleotide position 20, causing the proline (P) at amino acid position 7 to be replaced by an arginine (R). 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
0.65
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T;.
Eigen
Pathogenic
0.72
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Pathogenic
0.74
D
MetaRNN
Pathogenic
0.82
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.8
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-5.2
D;D
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;D
Vest4
0.73
MutPred
0.35
Loss of glycosylation at P7 (P = 0.032);Loss of glycosylation at P7 (P = 0.032);
MVP
0.45
MPC
1.0
ClinPred
0.96
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.87
gMVP
0.55

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755080861; hg19: chr5-167719177; API