13-114250575-A-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001078645.3(CDC16):c.998A>G(p.Tyr333Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
CDC16
NM_001078645.3 missense
NM_001078645.3 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 6.72
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC16 | NM_001078645.3 | c.998A>G | p.Tyr333Cys | missense_variant | 12/18 | ENST00000356221.8 | |
LOC105370384 | XR_007063887.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC16 | ENST00000356221.8 | c.998A>G | p.Tyr333Cys | missense_variant | 12/18 | 1 | NM_001078645.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152090Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251478Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135914
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461734Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727176
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74296
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.998A>G (p.Y333C) alteration is located in exon 12 (coding exon 12) of the CDC16 gene. This alteration results from a A to G substitution at nucleotide position 998, causing the tyrosine (Y) at amino acid position 333 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;T;T;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;.;D;D;.
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
M;.;M;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;.;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
D;.;D;.;D;.;.
Vest4
MutPred
Loss of disorder (P = 0.0864);.;Loss of disorder (P = 0.0864);.;.;.;.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at