5-138206633-C-G

Variant names:

• chr5-138206633-C-G
• rs1028052987
• NM_004661.4:c.286G>C

Variant summary

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

The NM_004661.4(CDC23):​c.286G>C​(p.Val96Leu) 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. 13/22 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. V96I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDC23 NM_004661.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.94
• Publications: 0 publications found

Genes affected

CDC23 (HGNC:1724): (cell division cycle 23) The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae Cdc23, a protein essential for cell cycle progression through the G2/M transition. This protein is a component of anaphase-promoting complex (APC), which is composed of eight protein subunits and highly conserved in eukaryotic cells. APC catalyzes the formation of cyclin B-ubiquitin conjugate that is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. This protein and 3 other members of the APC complex contain the TPR (tetratricopeptide repeat), a protein domain important for protein-protein interaction. [provided by RefSeq, Jul 2008]

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=0.12228927).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004661.4. 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
	CDC23	NM_004661.4	MANE Select	c.286G>C	p.Val96Leu	missense	Exon 3 of 16	NP_004652.2	Q9UJX2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC23	ENST00000394886.7	TSL:1 MANE Select	c.286G>C	p.Val96Leu	missense	Exon 3 of 16	ENSP00000378350.2	Q9UJX2-1
	CDC23	ENST00000394884.7	TSL:1	c.286G>C	p.Val96Leu	missense	Exon 3 of 3	ENSP00000378348.3	Q9UJX2-2
	CDC23	ENST00000892742.1		c.286G>C	p.Val96Leu	missense	Exon 3 of 16	ENSP00000562801.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251390 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.24
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		5.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.080
Sift	Benign	0.71	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.61		Gain of ubiquitination at K91 (P = 0.0982)
MVP		0.38
MPC		0.77
ClinPred		0.66	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.20
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: rs1028052987; hg19: chr5-137542322;