chr5-138189661-C-A

Position:

• chr5-138189661-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004661.4(CDC23):​c.1595G>T​(p.Cys532Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDC23 NM_004661.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55

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]

CDC23 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34577626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC23	NM_004661.4	c.1595G>T	p.Cys532Phe	missense_variant	15/16	ENST00000394886.7	NP_004652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC23	ENST00000394886.7	c.1595G>T	p.Cys532Phe	missense_variant	15/16	1	NM_004661.4	ENSP00000378350.2
CDC23	ENST00000464806.1	n.372G>T		non_coding_transcript_exon_variant	2/3	2
CDC23	ENST00000475021.1	n.410G>T		non_coding_transcript_exon_variant	1/2	2
CDC23	ENST00000471692.1	n.*9G>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.1595G>T (p.C532F) alteration is located in exon 15 (coding exon 15) of the CDC23 gene. This alteration results from a G to T substitution at nucleotide position 1595, causing the cysteine (C) at amino acid position 532 to be replaced by a phenylalanine (F). 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	0.33
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.088
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.24
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Polyphen		0.0010	B
Vest4		0.77
MutPred		0.48		Gain of ubiquitination at K535 (P = 0.1235);
MVP		0.84
MPC		1.2
ClinPred		0.74	D
GERP RS		5.1
Varity_R		0.56
gMVP		0.72

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-137525350;