3-46922254-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001277074.2(CCDC12):​c.400G>T​(p.Ala134Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CCDC12
NM_001277074.2 missense

Scores

7
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.41
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC12NM_001277074.2 linkc.400G>T p.Ala134Ser missense_variant Exon 6 of 7 ENST00000683445.1 NP_001264003.1 Q8WUD4
CCDC12NM_144716.6 linkc.439G>T p.Ala147Ser missense_variant Exon 7 of 8 NP_653317.2 J3KR35
CCDC12NR_102269.2 linkn.453G>T non_coding_transcript_exon_variant Exon 6 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC12ENST00000683445.1 linkc.400G>T p.Ala134Ser missense_variant Exon 6 of 7 NM_001277074.2 ENSP00000508011.1 Q8WUD4
CCDC12ENST00000292314.6 linkc.439G>T p.Ala147Ser missense_variant Exon 7 of 8 5 ENSP00000292314.2 J3KR35
CCDC12ENST00000425441.5 linkc.400G>T p.Ala134Ser missense_variant Exon 8 of 9 5 ENSP00000416263.2 Q8WUD4
CCDC12ENST00000604367.1 linkn.1906G>T non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.439G>T (p.A147S) alteration is located in exon 6 (coding exon 6) of the CCDC12 gene. This alteration results from a G to T substitution at nucleotide position 439, causing the alanine (A) at amino acid position 147 to be replaced by a serine (S). 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
0.30
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.30
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.028
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Uncertain
0.030
D
MutationAssessor
Pathogenic
3.6
H;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.70
N;D
REVEL
Pathogenic
0.72
Sift
Benign
0.40
T;D
Sift4G
Benign
0.062
T;T
Polyphen
0.99
D;.
Vest4
0.86
MutPred
0.78
Gain of glycosylation at T131 (P = 0.0064);.;
MVP
0.55
MPC
0.67
ClinPred
0.97
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.57
gMVP
0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-46963744; API