1-93207298-G-A

Variant summary

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

The NM_001378204.1(CCDC18):​c.1109G>A​(p.Arg370His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,428 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 (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

CCDC18
NM_001378204.1 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91
Variant links:
Genes affected
CCDC18 (HGNC:30370): (coiled-coil domain containing 18)

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=0.122422904).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC18NM_001378204.1 linkc.1109G>A p.Arg370His missense_variant 9/29 ENST00000690025.1 NP_001365133.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC18ENST00000690025.1 linkc.1109G>A p.Arg370His missense_variant 9/29 NM_001378204.1 ENSP00000510597.1 A0A8I5KWA2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152048
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000401
AC:
10
AN:
249272
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135248
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000531
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000424
AC:
62
AN:
1461262
Hom.:
0
Cov.:
31
AF XY:
0.0000371
AC XY:
27
AN XY:
726950
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000468
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000823
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000497
AC:
6

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 GeneticsSep 03, 2024The c.1109G>A (p.R370H) alteration is located in exon 9 (coding exon 8) of the CCDC18 gene. This alteration results from a G to A substitution at nucleotide position 1109, causing the arginine (R) at amino acid position 370 to be replaced by a histidine (H). 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
0.087
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.040
T;.;T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.9
M;.;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.091
Sift
Uncertain
0.021
D;D;D
Sift4G
Benign
0.16
T;T;T
Polyphen
1.0
D;.;.
Vest4
0.19
MVP
0.13
ClinPred
0.26
T
GERP RS
4.8
Varity_R
0.056
gMVP
0.14

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: rs185365289; hg19: chr1-93672855; API