5-55143536-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170402.1(CDC20B):c.463G>C(p.Glu155Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDC20B NM_001170402.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.109

Genes affected

CDC20B (HGNC:24222): (cell division cycle 20B) Predicted to enable anaphase-promoting complex binding activity and ubiquitin ligase activator activity. Predicted to be involved in anaphase-promoting complex-dependent catabolic process and positive regulation of anaphase-promoting complex-dependent catabolic process. Predicted to be part of anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09562561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC20B	NM_001170402.1	c.463G>C	p.Glu155Gln	missense_variant	4/12	ENST00000381375.7
CDC20B	NM_152623.2	c.463G>C	p.Glu155Gln	missense_variant	4/12
CDC20B	NM_001145734.2	c.463G>C	p.Glu155Gln	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC20B	ENST00000381375.7	c.463G>C	p.Glu155Gln	missense_variant	4/12	1	NM_001170402.1	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451618 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Sep 29, 2023

The c.463G>C (p.E155Q) alteration is located in exon 4 (coding exon 4) of the CDC20B gene. This alteration results from a G to C substitution at nucleotide position 463, causing the glutamic acid (E) at amino acid position 155 to be replaced by a glutamine (Q). 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	0.093
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	11
Dann	Uncertain	0.99
Eigen	Benign	-0.038
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	0.97	N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.71	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.96	D;P;P
Vest4		0.070
MutPred		0.40		Gain of MoRF binding (P = 0.0208);Gain of MoRF binding (P = 0.0208);Gain of MoRF binding (P = 0.0208);
MVP		0.18
MPC		0.34
ClinPred		0.41	T
GERP RS		2.8
Varity_R		0.077
gMVP		0.076

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: chr5-54439364;