17-73285453-C-T

Position:

• chr17-73285453-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012121.5(CDC42EP4):​c.1048G>A​(p.Glu350Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDC42EP4 NM_012121.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

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]

ACMG classification

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=0.24844715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42EP4	NM_012121.5	c.1048G>A	p.Glu350Lys	missense_variant	2/2	ENST00000335793.4	NP_036253.2
CDC42EP4	XM_005257182.3	c.1048G>A	p.Glu350Lys	missense_variant	2/2		XP_005257239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42EP4	ENST00000335793.4	c.1048G>A	p.Glu350Lys	missense_variant	2/2	1	NM_012121.5	ENSP00000338258.3
CDC42EP4	ENST00000439510.2	c.838G>A	p.Glu280Lys	missense_variant	3/3	2		ENSP00000404270.2
CDC42EP4	ENST00000581014.1	c.*5G>A		3_prime_UTR_variant	3/3	5		ENSP00000464104.1
CDC42EP4	ENST00000630622.1	c.*5G>A		downstream_gene_variant		5		ENSP00000485861.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.1048G>A (p.E350K) alteration is located in exon 2 (coding exon 1) of the CDC42EP4 gene. This alteration results from a G to A substitution at nucleotide position 1048, causing the glutamic acid (E) at amino acid position 350 to be replaced by a lysine (K). 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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.96	P;.
Vest4		0.36
MutPred		0.29		Gain of ubiquitination at E350 (P = 0.0037);.;
MVP		0.43
MPC		0.53
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-71281592;