chr2-37646324-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006449.5(CDC42EP3):c.264C>A(p.Asn88Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,058 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
CDC42EP3
NM_006449.5 missense
NM_006449.5 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 3.42
Genes affected
CDC42EP3 (HGNC:16943): (CDC42 effector protein 3) This gene encodes a member of a small family of guanosine triphosphate (GTP) metabolizing proteins that contain a CRIB (Cdc42, Rac interactive binding) domain. Members of this family of proteins act as effectors of CDC42 function. The encoded protein is involved in actin cytoskeleton re-organization during cell shape changes, including pseudopodia formation. A pseudogene of this gene is found on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21579671).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC42EP3 | NM_006449.5 | c.264C>A | p.Asn88Lys | missense_variant | 2/2 | ENST00000295324.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC42EP3 | ENST00000295324.4 | c.264C>A | p.Asn88Lys | missense_variant | 2/2 | 1 | NM_006449.5 | P1 | |
ENST00000702971.1 | n.105-15291G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
152188
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251358Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135842
GnomAD3 exomes
AF:
AC:
4
AN:
251358
Hom.:
AF XY:
AC XY:
4
AN XY:
135842
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727232
GnomAD4 exome
AF:
AC:
17
AN:
1461870
Hom.:
Cov.:
32
AF XY:
AC XY:
11
AN XY:
727232
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
GnomAD4 genome
AF:
AC:
1
AN:
152188
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74340
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
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 | Apr 28, 2022 | The c.264C>A (p.N88K) alteration is located in exon 2 (coding exon 1) of the CDC42EP3 gene. This alteration results from a C to A substitution at nucleotide position 264, causing the asparagine (N) at amino acid position 88 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Benign
.;T;T
Sift4G
Benign
T;T;.
Polyphen
D;D;.
Vest4
MutPred
Gain of ubiquitination at N88 (P = 0.0069);Gain of ubiquitination at N88 (P = 0.0069);Gain of ubiquitination at N88 (P = 0.0069);
MVP
MPC
0.42
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at