2-37646311-A-C

Variant names:

• chr2-37646311-A-C
• rs775860033
• NM_006449.5:c.277T>G

Variant summary

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

The NM_006449.5(CDC42EP3):​c.277T>G​(p.Ser93Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S93P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC42EP3 NM_006449.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

Genes affected

CDC42EP3 (HGNC:16943): (CDC42 effector protein 3) This gene encodes a member of a small family of guanosine triphosphate (GTP) metabolizing proteins that contain a CRIB (Cdc42, Rac interactive binding) domain. Members of this family of proteins act as effectors of CDC42 function. The encoded protein is involved in actin cytoskeleton re-organization during cell shape changes, including pseudopodia formation. A pseudogene of this gene is found on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

CDC42EP3-AS1 (HGNC:56370): (CDC42EP3 antisense RNA 1)

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=0.10594192).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006449.5. 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
	CDC42EP3	NM_006449.5	MANE Select	c.277T>G	p.Ser93Ala	missense	Exon 2 of 2	NP_006440.2
	CDC42EP3	NM_001270436.2		c.277T>G	p.Ser93Ala	missense	Exon 2 of 2	NP_001257365.1	Q9UKI2
	CDC42EP3	NM_001270437.2		c.277T>G	p.Ser93Ala	missense	Exon 2 of 2	NP_001257366.1	Q9UKI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42EP3	ENST00000295324.4	TSL:1 MANE Select	c.277T>G	p.Ser93Ala	missense	Exon 2 of 2	ENSP00000295324.3	Q9UKI2
	CDC42EP3	ENST00000611976.1	TSL:3	c.277T>G	p.Ser93Ala	missense	Exon 2 of 2	ENSP00000480549.1	Q9UKI2
	CDC42EP3	ENST00000885380.1		c.277T>G	p.Ser93Ala	missense	Exon 2 of 2	ENSP00000555439.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.038
Sift	Benign	0.45	T
Sift4G	Benign	1.0	T
Polyphen		0.13	B
Vest4		0.057
MutPred		0.22		Loss of disorder (P = 0.0573)
MVP		0.42
MPC		0.096
ClinPred		0.64	D
GERP RS		4.7
Varity_R		0.089
gMVP		0.45
Mutation Taster		=85/15	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: rs775860033; hg19: chr2-37873454;