chr13-114236826-C-G

Variant names:

• chr13-114236826-C-G
• NM_001078645.3:c.131C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_001078645.3(CDC16):​c.131C>G​(p.Ala44Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000253 in 1,461,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: CDC16 NM_001078645.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.98
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914
• BS2: High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC16	NM_001078645.3	c.131C>G	p.Ala44Gly	missense_variant	Exon 3 of 18	ENST00000356221.8	NP_001072113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC16	ENST00000356221.8	c.131C>G	p.Ala44Gly	missense_variant	Exon 3 of 18	1	NM_001078645.3	ENSP00000348554.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461146 Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15 AN XY: 726912

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111618

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.131C>G (p.A44G) alteration is located in exon 3 (coding exon 3) of the CDC16 gene. This alteration results from a C to G substitution at nucleotide position 131, causing the alanine (A) at amino acid position 44 to be replaced by a glycine (G). 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	0.25
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D;D;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.;D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.2	M;M;.
PhyloP100		7.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.28
Sift	Benign	0.044	D;D;D
Sift4G	Benign	0.065	T;T;T
Polyphen		0.98	D;D;P
Vest4		0.72
MutPred		0.81		Loss of catalytic residue at A44 (P = 0.1816);Loss of catalytic residue at A44 (P = 0.1816);.;
MVP		0.36
MPC		2.3
ClinPred		0.97	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.79
gMVP		0.58
Mutation Taster		=216/84	polymorphism

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

hg19: chr13-115002301;