chr3-46976753-C-G

Variant summary

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

The NM_144716.6(CCDC12):ā€‹c.19G>Cā€‹(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CCDC12
NM_144716.6 missense

Scores

1
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01
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=0.1331054).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC12NM_144716.6 linkuse as main transcriptc.19G>C p.Gly7Arg missense_variant 2/8 NP_653317.2
CCDC12NM_001277074.2 linkuse as main transcript upstream_gene_variant ENST00000683445.1 NP_001264003.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC12ENST00000683445.1 linkuse as main transcript upstream_gene_variant NM_001277074.2 ENSP00000508011 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.94e-7
AC:
1
AN:
1440484
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
714790
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000264

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 GeneticsAug 26, 2022The c.19G>C (p.G7R) 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 19, causing the glycine (G) at amino acid position 7 to be replaced by an arginine (R). 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
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
12
DANN
Uncertain
0.99
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.063
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.050
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.013
D
Vest4
0.41
MutPred
0.28
Gain of MoRF binding (P = 5e-04);
MVP
0.12
ClinPred
0.95
D
GERP RS
3.8
gMVP
0.054

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs777140774; hg19: chr3-47018243; API