22-37566405-C-T
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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
NM_152243.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 7.28
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]
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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 |
---|---|---|---|---|---|---|---|---|
CDC42EP1 | NM_152243.3 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
CDC42EP1 | ENST00000249014.5 | c.56C>T | p.Ser19Leu | missense_variant | 2/3 | 1 | NM_152243.3 | ENSP00000249014 | P1 | |
CDC42EP1 | ENST00000430687.1 | c.56C>T | p.Ser19Leu | missense_variant | 3/3 | 3 | ENSP00000411682 | |||
CDC42EP1 | ENST00000415670.1 | c.56C>T | p.Ser19Leu | missense_variant | 2/2 | 3 | ENSP00000405006 | |||
CDC42EP1 | ENST00000434728.1 | c.56C>T | p.Ser19Leu | missense_variant | 2/2 | 4 | ENSP00000403710 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152110Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000305 AC: 7AN: 229596Hom.: 0 AF XY: 0.0000401 AC XY: 5AN XY: 124554
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GnomAD4 exome AF: 0.0000256 AC: 37AN: 1445608Hom.: 0 Cov.: 33 AF XY: 0.0000251 AC XY: 18AN XY: 717642
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74300
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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 submitter | clinical testing | Ambry Genetics | Feb 17, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
P;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at