Variant 17-73285612-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012121.5(CDC42EP4):c.889C>T(p.Arg297Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000878 in 1,606,782 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 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

CDC42EP4
NM_012121.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

Variant links:

Genes affected

CDC42EP4 (HGNC:17147): (CDC42 effector protein 4) The product of this gene is a member of the CDC42-binding protein family. Members of this family interact with Rho family GTPases and regulate the organization of the actin cytoskeleton. This protein has been shown to bind both CDC42 and TC10 GTPases in a GTP-dependent manner. When overexpressed in fibroblasts, this protein was able to induce pseudopodia formation, which suggested a role in inducing actin filament assembly and cell shape control. [provided by RefSeq, Jul 2008]

CDC42EP4 links:

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=0.18622062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42EP4	NM_012121.5 linkuse as main transcript	c.889C>T	p.Arg297Cys	missense_variant	2/2	ENST00000335793.4	NP_036253.2
CDC42EP4	XM_005257182.3 linkuse as main transcript	c.889C>T	p.Arg297Cys	missense_variant	2/2		XP_005257239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42EP4	ENST00000335793.4 linkuse as main transcript	c.889C>T	p.Arg297Cys	missense_variant	2/2	1	NM_012121.5	ENSP00000338258	P1	Q9H3Q1-1
CDC42EP4	ENST00000439510.2 linkuse as main transcript	c.679C>T	p.Arg227Cys	missense_variant	3/3	2		ENSP00000404270		Q9H3Q1-2
CDC42EP4	ENST00000581014.1 linkuse as main transcript	c.118-32C>T		intron_variant		5		ENSP00000464104
CDC42EP4	ENST00000630622.1 linkuse as main transcript	c.118-32C>T		intron_variant		5		ENSP00000485861

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000705

AC:

AN:

241006

Hom.:

AF XY:

0.0000685

AC XY:

AN XY:

131410

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000830

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000887

AC:

129

AN:

1454574

Hom.:

Cov.:

AF XY:

0.0000954

AC XY:

AN XY:

722912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000850

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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 15, 2023

The c.889C>T (p.R297C) alteration is located in exon 2 (coding exon 1) of the CDC42EP4 gene. This alteration results from a C to T substitution at nucleotide position 889, causing the arginine (R) at amino acid position 297 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.15

MVP

0.59

MPC

0.38

ClinPred

0.18

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over