19-54465109-C-T

Variant names:

• chr19-54465109-C-T
• NM_145057.4:c.439G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145057.4(CDC42EP5):​c.439G>A​(p.Gly147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000573 in 1,222,162 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: CDC42EP5 NM_145057.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.984
• Publications: 0 publications found

Genes affected

CDC42EP5 (HGNC:17408): (CDC42 effector protein 5) Cell division control protein 42 (CDC42), a small Rho GTPase, regulates the formation of F-actin-containing structures through its interaction with the downstream effector proteins. The protein encoded by this gene is a member of the Borg (binder of Rho GTPases) family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to CDC42 and regulate its function negatively. The encoded protein may inhibit c-Jun N-terminal kinase (JNK) independently of CDC42 binding. The protein may also play a role in septin organization and inducing pseudopodia formation in fibroblasts [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20775354).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145057.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42EP5	NM_145057.4	MANE Select	c.439G>A	p.Gly147Ser	missense	Exon 3 of 3	NP_659494.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42EP5	ENST00000301200.3	TSL:1 MANE Select	c.439G>A	p.Gly147Ser	missense	Exon 3 of 3	ENSP00000301200.2	Q6NZY7
	CDC42EP5	ENST00000870796.1		c.439G>A	p.Gly147Ser	missense	Exon 2 of 2	ENSP00000540855.1
	CDC42EP5	ENST00000912085.1		c.439G>A	p.Gly147Ser	missense	Exon 2 of 2	ENSP00000582144.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000573 AC: 7 AN: 1222162 Hom.: 0 Cov.: 31 AF XY: 0.00000672 AC XY: 4 AN XY: 595624

African (AFR) AF: 0.00 AC: 0 AN: 24450

American (AMR) AF: 0.00 AC: 0 AN: 13336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16532

East Asian (EAS) AF: 0.00 AC: 0 AN: 28660

South Asian (SAS) AF: 0.00 AC: 0 AN: 52622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4770

European-Non Finnish (NFE) AF: 0.00000701 AC: 7 AN: 998904

Other (OTH) AF: 0.00 AC: 0 AN: 49566

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.65	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.98
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.065
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.21
MutPred		0.27		Loss of catalytic residue at L148 (P = 0.0573)
MVP		0.55
MPC		2.0
ClinPred		0.63	D
GERP RS		2.8
Varity_R		0.24
gMVP		0.18
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

hg19: chr19-54976293;