11-65083969-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080668.4(CDCA5):​c.10A>G​(p.Arg4Gly) 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: 35)

Consequence

CDCA5
NM_080668.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.766
Variant links:
Genes affected
CDCA5 (HGNC:14626): (cell division cycle associated 5) Predicted to enable chromatin binding activity. Involved in double-strand break repair; mitotic sister chromatid segregation; and regulation of cell cycle process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
ZFPL1 (HGNC:12868): (zinc finger protein like 1) Predicted to enable metal ion binding activity. Predicted to be involved in vesicle-mediated transport. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2391302).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDCA5NM_080668.4 linkc.10A>G p.Arg4Gly missense_variant Exon 1 of 6 ENST00000275517.8 NP_542399.1 Q96FF9A0A024R5D6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDCA5ENST00000275517.8 linkc.10A>G p.Arg4Gly missense_variant Exon 1 of 6 1 NM_080668.4 ENSP00000275517.3 Q96FF9

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
35

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.10A>G (p.R4G) alteration is located in exon 1 (coding exon 1) of the CDCA5 gene. This alteration results from a A to G substitution at nucleotide position 10, causing the arginine (R) at amino acid position 4 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
0.043
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.8
M;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-4.2
D;D
REVEL
Benign
0.20
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
0.58
P;.
Vest4
0.24
MutPred
0.57
Loss of methylation at R4 (P = 0.0223);Loss of methylation at R4 (P = 0.0223);
MVP
0.73
MPC
1.5
ClinPred
0.99
D
GERP RS
1.7
Varity_R
0.32
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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: chr11-64851441; API