3-46922265-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001277074.2(CCDC12):c.389G>A(p.Arg130Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000245 in 1,614,158 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: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
CCDC12
NM_001277074.2 missense
NM_001277074.2 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 6.41
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC12 | NM_001277074.2 | c.389G>A | p.Arg130Gln | missense_variant | 6/7 | ENST00000683445.1 | |
CCDC12 | NM_144716.6 | c.428G>A | p.Arg143Gln | missense_variant | 7/8 | ||
CCDC12 | NR_102269.2 | n.442G>A | non_coding_transcript_exon_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC12 | ENST00000683445.1 | c.389G>A | p.Arg130Gln | missense_variant | 6/7 | NM_001277074.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152266Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000107 AC: 27AN: 251476Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135910
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GnomAD4 exome AF: 0.000254 AC: 371AN: 1461892Hom.: 0 Cov.: 33 AF XY: 0.000245 AC XY: 178AN XY: 727246
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74390
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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 | Mar 25, 2024 | The c.428G>A (p.R143Q) alteration is located in exon 6 (coding exon 6) of the CCDC12 gene. This alteration results from a G to A substitution at nucleotide position 428, causing the arginine (R) at amino acid position 143 to be replaced by a glutamine (Q). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D
REVEL
Pathogenic
Sift
Uncertain
.;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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