1-93264823-T-G

Variant names:

• chr1-93264823-T-G
• NM_001378204.1:c.3807T>G
• CCDC18 p.Asp1269Glu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378204.1(CCDC18):​c.3807T>G​(p.Asp1269Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC18 NM_001378204.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11231926).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378204.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC18	NM_001378204.1	MANE Select	c.3807T>G	p.Asp1269Glu	missense	Exon 27 of 29	NP_001365133.1	A0A8I5KWA2
	CCDC18	NM_001306076.1		c.3804T>G	p.Asp1268Glu	missense	Exon 27 of 29	NP_001293005.1	Q6PH87
	CCDC18	NM_206886.4		c.3807T>G	p.Asp1269Glu	missense	Exon 27 of 28	NP_996769.3	Q6PH87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC18	ENST00000690025.1	MANE Select	c.3807T>G	p.Asp1269Glu	missense	Exon 27 of 29	ENSP00000510597.1	A0A8I5KWA2
	CCDC18	ENST00000401026.7	TSL:1	c.3807T>G	p.Asp1269Glu	missense	Exon 27 of 28	ENSP00000383808.3	E9PFB9
	CCDC18	ENST00000447456.1	TSL:1	n.563T>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.49
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.13
Sift	Benign	0.29	T
Sift4G	Benign	0.51	T
Varity_R		0.030
gMVP		0.056
Mutation Taster		=99/1	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-93730380;