rs839763

Variant names:

• chr1-43359973-T-C
• rs839763
• NM_001255.3:c.432T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001255.3(CDC20):​c.432T>C​(p.Tyr144Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,613,612 control chromosomes in the GnomAD database, including 106,147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8486 hom., cov: 32)
  • Exomes 𝑓: 0.36 (97661 hom.)
• Consequence: CDC20 NM_001255.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 23 publications found

Genes affected

CDC20 (HGNC:1723): (cell division cycle 20) CDC20 appears to act as a regulatory protein interacting with several other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes, nuclear movement prior to anaphase and chromosome separation. [provided by RefSeq, Jul 2008]

CDC20 Gene-Disease associations (from GenCC):

• oocyte maturation defect 14

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.297 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC20	NM_001255.3	c.432T>C	p.Tyr144Tyr	synonymous_variant	Exon 5 of 11	ENST00000310955.11	NP_001246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC20	ENST00000310955.11	c.432T>C	p.Tyr144Tyr	synonymous_variant	Exon 5 of 11	1	NM_001255.3	ENSP00000308450.5
CDC20	ENST00000372462.1	c.432T>C	p.Tyr144Tyr	synonymous_variant	Exon 4 of 10	1		ENSP00000361540.1
CDC20	ENST00000478882.1	n.207T>C		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49746 AN: 151976 Hom.: 8483 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.379

GnomAD2 exomes AF: 0.310 AC: 78054 AN: 251382 AF XY: 0.308

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.0947

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.350

GnomAD4 exome AF: 0.358 AC: 522899 AN: 1461518 Hom.: 97661 Cov.: 40 AF XY: 0.352 AC XY: 256284 AN XY: 727052

African (AFR) AF: 0.280 AC: 9379 AN: 33472

American (AMR) AF: 0.316 AC: 14146 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 10723 AN: 26130

East Asian (EAS) AF: 0.116 AC: 4600 AN: 39700

South Asian (SAS) AF: 0.158 AC: 13586 AN: 86244

European-Finnish (FIN) AF: 0.324 AC: 17297 AN: 53394

Middle Eastern (MID) AF: 0.391 AC: 2257 AN: 5768

European-Non Finnish (NFE) AF: 0.387 AC: 429899 AN: 1111698

Other (OTH) AF: 0.348 AC: 21012 AN: 60388

GnomAD4 genome AF: 0.327 AC: 49777 AN: 152094 Hom.: 8486 Cov.: 32 AF XY: 0.323 AC XY: 23988 AN XY: 74360

African (AFR) AF: 0.272 AC: 11293 AN: 41482

American (AMR) AF: 0.373 AC: 5694 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3472

East Asian (EAS) AF: 0.0982 AC: 509 AN: 5182

South Asian (SAS) AF: 0.149 AC: 717 AN: 4814

European-Finnish (FIN) AF: 0.332 AC: 3507 AN: 10572

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25379 AN: 67982

Other (OTH) AF: 0.377 AC: 796 AN: 2110

Alfa AF: 0.361 Hom.: 8117

Bravo AF: 0.330

Asia WGS AF: 0.146 AC: 510 AN: 3478

EpiCase AF: 0.385

EpiControl AF: 0.386

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs839763; hg19: chr1-43825644; COSMIC: COSV60521684; COSMIC: COSV60521684;