chr3-46922071-A-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.487T>Cā€‹(p.Cys163Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CCDC12
NM_001277074.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15
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=0.11095688).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC12NM_001277074.2 linkuse as main transcriptc.487T>C p.Cys163Arg missense_variant 7/7 ENST00000683445.1 NP_001264003.1
CCDC12NM_144716.6 linkuse as main transcriptc.526T>C p.Cys176Arg missense_variant 8/8 NP_653317.2
CCDC12NR_102269.2 linkuse as main transcriptn.540T>C non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC12ENST00000683445.1 linkuse as main transcriptc.487T>C p.Cys163Arg missense_variant 7/7 NM_001277074.2 ENSP00000508011 P1
CCDC12ENST00000292314.6 linkuse as main transcriptc.526T>C p.Cys176Arg missense_variant 8/85 ENSP00000292314
CCDC12ENST00000425441.5 linkuse as main transcriptc.487T>C p.Cys163Arg missense_variant 9/95 ENSP00000416263 P1
CCDC12ENST00000604367.1 linkuse as main transcriptn.2089T>C non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251456
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461778
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 GeneticsMar 21, 2023The c.526T>C (p.C176R) alteration is located in exon 7 (coding exon 7) of the CCDC12 gene. This alteration results from a T to C substitution at nucleotide position 526, causing the cysteine (C) at amino acid position 176 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
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
16
DANN
Benign
0.72
DEOGEN2
Benign
0.010
T;.
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.040
.;N
REVEL
Benign
0.15
Sift
Benign
0.39
.;T
Sift4G
Benign
0.38
T;T
Polyphen
0.048
B;.
Vest4
0.28
MutPred
0.15
Gain of glycosylation at S165 (P = 0.0223);.;
MVP
0.12
MPC
0.42
ClinPred
0.043
T
GERP RS
1.8
Varity_R
0.22
gMVP
0.042

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: rs774413430; hg19: chr3-46963561; API