1-93264875-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001378204.1(CCDC18):​c.3859G>C​(p.Ala1287Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,386 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1287T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CCDC18
NM_001378204.1 missense

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.10
Variant links:
Genes affected
CCDC18 (HGNC:30370): (coiled-coil domain containing 18)
CCDC18-AS1 (HGNC:52262): (CCDC18 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC18NM_001378204.1 linkc.3859G>C p.Ala1287Pro missense_variant Exon 27 of 29 ENST00000690025.1 NP_001365133.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC18ENST00000690025.1 linkc.3859G>C p.Ala1287Pro missense_variant Exon 27 of 29 NM_001378204.1 ENSP00000510597.1 A0A8I5KWA2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459386
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
726206
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.059
T;.
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.0027
T
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.21
Sift
Uncertain
0.0070
D;D
Sift4G
Benign
0.13
T;T
Vest4
0.55
MVP
0.51
ClinPred
0.92
D
GERP RS
5.2
Varity_R
0.76
gMVP
0.40

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: chr1-93730432; API