chr3-46976699-C-G

Variant summary

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

The NM_001277074.2(CCDC12):ā€‹c.34G>Cā€‹(p.Glu12Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000449 in 1,604,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00013 ( 0 hom., cov: 35)
Exomes š‘“: 0.000036 ( 0 hom. )

Consequence

CCDC12
NM_001277074.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28
Variant links:
Genes affected
CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [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=0.20954445).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC12NM_001277074.2 linkuse as main transcriptc.34G>C p.Glu12Gln missense_variant 1/7 ENST00000683445.1 NP_001264003.1
CCDC12NM_144716.6 linkuse as main transcriptc.73G>C p.Glu25Gln missense_variant 2/8 NP_653317.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC12ENST00000683445.1 linkuse as main transcriptc.34G>C p.Glu12Gln missense_variant 1/7 NM_001277074.2 ENSP00000508011 P1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152256
Hom.:
0
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000981
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000260
AC:
6
AN:
230434
Hom.:
0
AF XY:
0.0000160
AC XY:
2
AN XY:
125070
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000915
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000292
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000358
AC:
52
AN:
1452440
Hom.:
0
Cov.:
56
AF XY:
0.0000236
AC XY:
17
AN XY:
721854
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000229
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000316
Gnomad4 OTH exome
AF:
0.000117
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152256
Hom.:
0
Cov.:
35
AF XY:
0.000108
AC XY:
8
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000981
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000135
Hom.:
1
Bravo
AF:
0.000253
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000248
AC:
3

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 submitterclinical testingAmbry GeneticsNov 13, 2023The c.73G>C (p.E25Q) alteration is located in exon 1 (coding exon 1) of the CCDC12 gene. This alteration results from a G to C substitution at nucleotide position 73, causing the glutamic acid (E) at amino acid position 25 to be replaced by a glutamine (Q). 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
0.19
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.029
T;.;T;T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Benign
0.30
N
LIST_S2
Uncertain
0.87
D;D;T;T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.21
T;T;T;T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
0.49
N;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.4
.;N;.;.
REVEL
Benign
0.14
Sift
Benign
0.25
.;T;.;.
Sift4G
Benign
0.25
T;T;T;.
Polyphen
1.0
D;.;.;.
Vest4
0.37
MVP
0.40
MPC
0.23
ClinPred
0.40
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs147840111; hg19: chr3-47018189; API