1-93201936-T-C

Position:

• chr1-93201936-T-C

Variant summary

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

The NM_001378204.1(CCDC18):​c.743T>C​(p.Leu248Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC18 NM_001378204.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20

Genes affected

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

ACMG classification

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/exons	MANE	Protein	UniProt
CCDC18	NM_001378204.1	c.743T>C	p.Leu248Pro	missense_variant	7/29	ENST00000690025.1	NP_001365133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC18	ENST00000690025.1	c.743T>C	p.Leu248Pro	missense_variant	7/29		NM_001378204.1	ENSP00000510597.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.743T>C (p.L248P) alteration is located in exon 7 (coding exon 6) of the CCDC18 gene. This alteration results from a T to C substitution at nucleotide position 743, causing the leucine (L) at amino acid position 248 to be replaced by a proline (P). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-4.4	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.080	T;T
Vest4		0.91
MVP		0.35
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.86
gMVP		0.72

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: chr1-93667493;