NM_145057.4:c.395C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145057.4(CDC42EP5):​c.395C>A​(p.Ala132Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CDC42EP5
NM_145057.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

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: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16456431).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDC42EP5NM_145057.4 linkc.395C>A p.Ala132Asp 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.395C>A p.Ala132Asp missense_variant Exon 3 of 3 1 NM_145057.4 ENSP00000301200.2 Q6NZY7

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152076
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1255200
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
615234
African (AFR)
AF:
0.00
AC:
0
AN:
25038
American (AMR)
AF:
0.00
AC:
0
AN:
14822
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
17952
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28920
South Asian (SAS)
AF:
0.00
AC:
0
AN:
58326
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33366
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4704
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1020592
Other (OTH)
AF:
0.00
AC:
0
AN:
51480
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152076
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74288
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41434
American (AMR)
AF:
0.00
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10578
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67984
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.395C>A (p.A132D) alteration is located in exon 3 (coding exon 1) of the CDC42EP5 gene. This alteration results from a C to A substitution at nucleotide position 395, causing the alanine (A) at amino acid position 132 to be replaced by an aspartic acid (D). 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
0.096
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.026
T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.25
N
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.97
L
PhyloP100
1.8
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.079
Sift
Uncertain
0.022
D
Sift4G
Benign
0.49
T
Polyphen
0.84
P
Vest4
0.26
MutPred
0.079
Loss of loop (P = 0.0986);
MVP
0.43
MPC
1.5
ClinPred
0.30
T
GERP RS
1.9
Varity_R
0.25
gMVP
0.20
Mutation Taster
=93/7
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: rs1163847204; hg19: chr19-54976337; API