NM_001378204.1:c.3854T>G

Variant names:

• chr1-93264870-T-G
• rs199565263
• NM_001378204.1:c.3854T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001378204.1(CCDC18):​c.3854T>G​(p.Ile1285Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,386 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. I1285T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC18 NM_001378204.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89
• Publications: 0 publications found

Genes affected

CCDC18 (HGNC:30370): (coiled-coil domain containing 18)

CCDC18-AS1 (HGNC:52262): (CCDC18 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC18	NM_001378204.1	c.3854T>G	p.Ile1285Ser	missense_variant	Exon 27 of 29	ENST00000690025.1	NP_001365133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC18	ENST00000690025.1	c.3854T>G	p.Ile1285Ser	missense_variant	Exon 27 of 29		NM_001378204.1	ENSP00000510597.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460386 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726624

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110830

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.0031	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;.
PhyloP100		4.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0020	D;D
Vest4		0.78
MVP		0.49
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.44
gMVP		0.42
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.59		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199565263; hg19: chr1-93730427; COSMIC: COSV100159691;