5-55128468-T-C

Variant summary

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

The NM_001170402.1(CDC20B):c.847A>G(p.Lys283Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,608,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: CDC20B NM_001170402.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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=0.06839353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC20B	NM_001170402.1	c.847A>G	p.Lys283Glu	missense_variant	7/12	ENST00000381375.7
CDC20B	NM_152623.2	c.847A>G	p.Lys283Glu	missense_variant	7/12
CDC20B	NM_001145734.2	c.847A>G	p.Lys283Glu	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC20B	ENST00000381375.7	c.847A>G	p.Lys283Glu	missense_variant	7/12	1	NM_001170402.1	A1
CDC20B	ENST00000296733.5	c.847A>G	p.Lys283Glu	missense_variant	7/12	1		P4
CDC20B	ENST00000322374.10	c.847A>G	p.Lys283Glu	missense_variant	7/11	1
CDC20B	ENST00000513180.5	c.847A>G	p.Lys283Glu	missense_variant, NMD_transcript_variant	7/12	5

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000143 AC: 35 AN: 245132 Hom.: 0 AF XY: 0.000128 AC XY: 17 AN XY: 132536

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000139

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000241

Gnomad OTH exome AF: 0.000501

GnomAD4 exome AF: 0.000184 AC: 268 AN: 1456174 Hom.: 0 Cov.: 33 AF XY: 0.000177 AC XY: 128 AN XY: 724230

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.0000928

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000166

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000209

Gnomad4 OTH exome AF: 0.000283

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74326

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.000145 Hom.: 0

Bravo AF: 0.000174

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000165 AC: 20

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000416

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

Nov 13, 2023

The c.847A>G (p.K283E) alteration is located in exon 7 (coding exon 7) of the CDC20B gene. This alteration results from a A to G substitution at nucleotide position 847, causing the lysine (K) at amino acid position 283 to be replaced by a glutamic acid (E). 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	0.098
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	20
Dann	Uncertain	0.99
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.068	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.099	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.021	B;B;B
Vest4		0.15
MVP		0.14
MPC		0.29
ClinPred		0.049	T
GERP RS		4.6
Varity_R		0.17
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144412288; hg19: chr5-54424296;