22-37566405-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_152243.3(CDC42EP1):​c.56C>T​(p.Ser19Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,597,718 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

CDC42EP1
NM_152243.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28
Variant links:
Genes affected
CDC42EP1 (HGNC:17014): (CDC42 effector protein 1) CDC42 is a member of the Rho GTPase family that regulates multiple cellular activities, including actin polymerization. The protein encoded by this gene is a CDC42 binding protein that mediates actin cytoskeleton reorganization at the plasma membrane. This protein is secreted and is primarily found in bone marrow. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity BORG5_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26832825).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDC42EP1NM_152243.3 linkuse as main transcriptc.56C>T p.Ser19Leu missense_variant 2/3 ENST00000249014.5 NP_689449.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDC42EP1ENST00000249014.5 linkuse as main transcriptc.56C>T p.Ser19Leu missense_variant 2/31 NM_152243.3 ENSP00000249014 P1Q00587-1
CDC42EP1ENST00000430687.1 linkuse as main transcriptc.56C>T p.Ser19Leu missense_variant 3/33 ENSP00000411682
CDC42EP1ENST00000415670.1 linkuse as main transcriptc.56C>T p.Ser19Leu missense_variant 2/23 ENSP00000405006
CDC42EP1ENST00000434728.1 linkuse as main transcriptc.56C>T p.Ser19Leu missense_variant 2/24 ENSP00000403710

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
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
GnomAD3 exomes
AF:
0.0000305
AC:
7
AN:
229596
Hom.:
0
AF XY:
0.0000401
AC XY:
5
AN XY:
124554
show subpopulations
Gnomad AFR exome
AF:
0.0000687
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000580
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000483
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000256
AC:
37
AN:
1445608
Hom.:
0
Cov.:
33
AF XY:
0.0000251
AC XY:
18
AN XY:
717642
show subpopulations
Gnomad4 AFR exome
AF:
0.000241
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000513
Gnomad4 SAS exome
AF:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000181
Gnomad4 OTH exome
AF:
0.000100
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152110
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000965
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000174
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsFeb 17, 2024The c.56C>T (p.S19L) alteration is located in exon 2 (coding exon 1) of the CDC42EP1 gene. This alteration results from a C to T substitution at nucleotide position 56, causing the serine (S) at amino acid position 19 to be replaced by a leucine (L). 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
0.21
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.064
T;T;T;T
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.27
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;.;.;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
0.55
N;N;N;D
REVEL
Benign
0.092
Sift
Uncertain
0.0050
D;D;D;D
Sift4G
Benign
0.096
T;T;T;T
Polyphen
0.91
P;.;.;.
Vest4
0.41
MVP
0.70
MPC
0.26
ClinPred
0.35
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.18
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs368492182; hg19: chr22-37962412; COSMIC: COSV50756221; COSMIC: COSV50756221; API