rs1258130123

Variant names:

• chr19-54465348-G-C
• rs1258130123
• NM_145057.4:c.200C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-54465348-G-C
• chr19-54465348-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145057.4(CDC42EP5):​c.200C>G​(p.Ala67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000593 in 1,011,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A67D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: CDC42EP5 NM_145057.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.101
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09836486).

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.200C>G	p.Ala67Gly	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.200C>G	p.Ala67Gly	missense	Exon 3 of 3	ENSP00000301200.2	Q6NZY7
	CDC42EP5	ENST00000870796.1		c.200C>G	p.Ala67Gly	missense	Exon 2 of 2	ENSP00000540855.1
	CDC42EP5	ENST00000912085.1		c.200C>G	p.Ala67Gly	missense	Exon 2 of 2	ENSP00000582144.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000593 AC: 6 AN: 1011696 Hom.: 0 Cov.: 27 AF XY: 0.00000630 AC XY: 3 AN XY: 476498

African (AFR) AF: 0.00 AC: 0 AN: 20254

American (AMR) AF: 0.00 AC: 0 AN: 6246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11312

East Asian (EAS) AF: 0.00 AC: 0 AN: 20500

South Asian (SAS) AF: 0.000265 AC: 5 AN: 18874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2528

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 874950

Other (OTH) AF: 0.00 AC: 0 AN: 38626

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.072
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.14	N
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.10
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.035
Sift	Benign	0.067	T
Sift4G	Benign	0.45	T
Polyphen		0.46	P
Vest4		0.11
MutPred		0.22		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.21
MPC		0.87
ClinPred		0.17	T
GERP RS		1.2
Varity_R		0.11
gMVP		0.14
Mutation Taster		=93/7	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: rs1258130123; hg19: chr19-54976532;