rs1465526286

Variant names:

• chr19-54465186-G-A
• rs1465526286
• NM_145057.4:c.362C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-54465186-G-A
• chr19-54465186-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145057.4(CDC42EP5):​c.362C>T​(p.Ala121Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000699 in 1,430,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: CDC42EP5 NM_145057.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.107
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030202657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42EP5	NM_145057.4	c.362C>T	p.Ala121Val	missense_variant	Exon 3 of 3	ENST00000301200.3	NP_659494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42EP5	ENST00000301200.3	c.362C>T	p.Ala121Val	missense_variant	Exon 3 of 3	1	NM_145057.4	ENSP00000301200.2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151852 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000749 AC: 4 AN: 53388 AF XY: 0.0000318

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000491

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000626 AC: 8 AN: 1278518 Hom.: 0 Cov.: 31 AF XY: 0.00000636 AC XY: 4 AN XY: 628916

African (AFR) AF: 0.00 AC: 0 AN: 25522

American (AMR) AF: 0.000378 AC: 7 AN: 18524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20712

East Asian (EAS) AF: 0.00 AC: 0 AN: 28326

South Asian (SAS) AF: 0.00 AC: 0 AN: 64698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4622

European-Non Finnish (NFE) AF: 9.71e-7 AC: 1 AN: 1030036

Other (OTH) AF: 0.00 AC: 0 AN: 52670

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151852 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74164

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.000131 AC: 2 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67904

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.362C>T (p.A121V) alteration is located in exon 3 (coding exon 1) of the CDC42EP5 gene. This alteration results from a C to T substitution at nucleotide position 362, causing the alanine (A) at amino acid position 121 to be replaced by a valine (V). 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	0.072
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.062	N
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.11
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.021
Sift	Benign	0.23	T
Sift4G	Benign	0.12	T
Polyphen		0.0010	B
Vest4		0.039
MutPred		0.071		Gain of methylation at K118 (P = 0.1132);
MVP		0.14
MPC		0.86
ClinPred		0.041	T
GERP RS		-6.4
Varity_R		0.022
gMVP		0.097
Mutation Taster		=99/1	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

dbSNP: rs1465526286; hg19: chr19-54976370;