Genetic Variant CDC16:p.Ile132Ile (chr13-114242135-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001078645.3(CDC16):c.396C>T(p.Ile132Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,606,358 control chromosomes in the GnomAD database, including 278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 158 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 120 hom. )

Consequence

CDC16
NM_001078645.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.99

Variant links:

Genes affected

CDC16 (HGNC:1720): (cell division cycle 16) The protein encoded by this gene functions as a protein ubiquitin ligase and is a component of the multiprotein APC complex. The APC complex is a cyclin degradation system that governs exit from mitosis by targeting cell cycle proteins for degredation by the 26S proteasome. Each component protein of the APC complex is highly conserved among eukaryotic organisms. This protein, and other APC complex proteins, contain a tetratricopeptide repeat (TPR) domain; a protein domain that is often involved in protein-protein interactions and the assembly of multiprotein complexes. Multiple alternatively spliced transcript variants, encoding distinct proteins, have been identified. [provided by RefSeq, Jan 2016]

CDC16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 13-114242135-C-T is Benign according to our data. Variant chr13-114242135-C-T is described in ClinVar as [Benign]. Clinvar id is 773720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC16	NM_001078645.3 link	c.396C>T	p.Ile132Ile	synonymous_variant	Exon 6 of 18	ENST00000356221.8	NP_001072113.1	Q13042-1A0A024RDZ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC16	ENST00000356221.8 link	c.396C>T	p.Ile132Ile	synonymous_variant	Exon 6 of 18	1	NM_001078645.3	ENSP00000348554.3		Q13042-1

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3711

AN:

152120

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0854

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00897

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:

0.0000882

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00663

AC:

1615

AN:

243622

Hom.:

AF XY:

0.00489

AC XY:

643

AN XY:

131504

show subpopulations

Gnomad AFR exome

AF:

0.0903

Gnomad AMR exome

AF:

0.00377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000808

Gnomad OTH exome

AF:

0.00387

GnomAD4 exome

AF:

0.00231

AC:

3362

AN:

1454120

Hom.:

120

Cov.:

AF XY:

0.00193

AC XY:

1397

AN XY:

723144

show subpopulations

Gnomad4 AFR exome

AF:

0.0856

Gnomad4 AMR exome

AF:

0.00405

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000949

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.00519

GnomAD4 genome

AF:

0.0244

AC:

3716

AN:

152238

Hom.:

158

Cov.:

AF XY:

0.0236

AC XY:

1758

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0852

Gnomad4 AMR

AF:

0.00896

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00715

Hom.:

Bravo

AF:

0.0284

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

8.4

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over