5-55133454-G-A

Variant summary

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

The NM_001170402.1(CDC20B):c.655C>T(p.Pro219Ser) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: CDC20B NM_001170402.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2880935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC20B	NM_001170402.1	c.655C>T	p.Pro219Ser	missense_variant	6/12	ENST00000381375.7
CDC20B	NM_152623.2	c.655C>T	p.Pro219Ser	missense_variant	6/12
CDC20B	NM_001145734.2	c.655C>T	p.Pro219Ser	missense_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC20B	ENST00000381375.7	c.655C>T	p.Pro219Ser	missense_variant	6/12	1	NM_001170402.1	A1
CDC20B	ENST00000296733.5	c.655C>T	p.Pro219Ser	missense_variant	6/12	1		P4
CDC20B	ENST00000322374.10	c.655C>T	p.Pro219Ser	missense_variant	6/11	1
CDC20B	ENST00000513180.5	c.655C>T	p.Pro219Ser	missense_variant, NMD_transcript_variant	6/12	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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 14, 2022

The c.655C>T (p.P219S) alteration is located in exon 6 (coding exon 6) of the CDC20B gene. This alteration results from a C to T substitution at nucleotide position 655, causing the proline (P) at amino acid position 219 to be replaced by a serine (S). 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	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	0.55	D;D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.79	P;D;D
Vest4		0.21
MutPred		0.53		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.39
MPC		0.25
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.47
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr5-54429282;