NM_145057.4:c.277C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145057.4(CDC42EP5):​c.277C>G​(p.Leu93Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,353,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CDC42EP5
NM_145057.4 missense

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.745

Publications

0 publications found
Variant links:
Genes affected
CDC42EP5 (HGNC:17408): (CDC42 effector protein 5) Cell division control protein 42 (CDC42), a small Rho GTPase, regulates the formation of F-actin-containing structures through its interaction with the downstream effector proteins. The protein encoded by this gene is a member of the Borg (binder of Rho GTPases) family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to CDC42 and regulate its function negatively. The encoded protein may inhibit c-Jun N-terminal kinase (JNK) independently of CDC42 binding. The protein may also play a role in septin organization and inducing pseudopodia formation in fibroblasts [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07620731).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDC42EP5NM_145057.4 linkc.277C>G p.Leu93Val missense_variant Exon 3 of 3 ENST00000301200.3 NP_659494.2 Q6NZY7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDC42EP5ENST00000301200.3 linkc.277C>G p.Leu93Val missense_variant Exon 3 of 3 1 NM_145057.4 ENSP00000301200.2 Q6NZY7

Frequencies

GnomAD3 genomes
AF:
0.0000727
AC:
11
AN:
151386
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000263
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:
0.0000884
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000843
AC:
5
AN:
59312
AF XY:
0.0000279
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000392
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000997
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000138
AC:
166
AN:
1202118
Hom.:
0
Cov.:
31
AF XY:
0.000124
AC XY:
73
AN XY:
586740
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24678
American (AMR)
AF:
0.000204
AC:
3
AN:
14670
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18830
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27722
South Asian (SAS)
AF:
0.00
AC:
0
AN:
50942
European-Finnish (FIN)
AF:
0.0000335
AC:
1
AN:
29894
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3980
European-Non Finnish (NFE)
AF:
0.000159
AC:
156
AN:
983128
Other (OTH)
AF:
0.000124
AC:
6
AN:
48274
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.457
Heterozygous variant carriers
0
8
16
25
33
41
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000726
AC:
11
AN:
151494
Hom.:
0
Cov.:
32
AF XY:
0.0000810
AC XY:
6
AN XY:
74068
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41436
American (AMR)
AF:
0.000262
AC:
4
AN:
15248
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5136
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10258
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.0000885
AC:
6
AN:
67830
Other (OTH)
AF:
0.00
AC:
0
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.0000285
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 10, 2021
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.277C>G (p.L93V) alteration is located in exon 3 (coding exon 1) of the CDC42EP5 gene. This alteration results from a C to G substitution at nucleotide position 277, causing the leucine (L) at amino acid position 93 to be replaced by a valine (V). 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
Benign
0.14
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.044
T
Eigen
Benign
-0.041
Eigen_PC
Benign
-0.024
FATHMM_MKL
Benign
0.72
D
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.076
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
PhyloP100
0.74
PrimateAI
Pathogenic
0.95
D
PROVEAN
Benign
-0.85
N
REVEL
Benign
0.046
Sift
Uncertain
0.028
D
Sift4G
Benign
0.30
T
Polyphen
0.80
P
Vest4
0.032
MutPred
0.32
Loss of stability (P = 0.085);
MVP
0.31
MPC
2.0
ClinPred
0.093
T
GERP RS
3.1
Varity_R
0.11
gMVP
0.27
Mutation Taster
=79/21
polymorphism

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

Other links and lift over

dbSNP: rs555638947; hg19: chr19-54976455; API