rs2118041989

Variant names:

• chr9-78236404-C-G
• rs2118041989
• NM_001330691.3:c.54C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-78236404-C-G
• chr9-78236404-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330691.3(CEP78):​c.54C>G​(p.His18Gln) 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. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. H18Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP78 NM_001330691.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 0 publications found

Genes affected

CEP78 (HGNC:25740): (centrosomal protein 78) This gene encodes a centrosomal protein that is both required for the regulation of centrosome-related events during the cell cycle, and required for ciliogenesis. The encoded protein has an N-terminal leucine-rich repeat (LRR) domain with six consecutive LRR repeats, and a C-terminal coiled-coil domain. It interacts with the N-terminal catalytic domain of polo-like kinase 4 (PLK4) and colocalizes with PLK4 to the distal end of the centriole. Naturally occurring mutations in this gene cause defects in primary cilia that result in retinal degeneration and sensorineural hearing loss which are associated with cone-rod degeneration disease as well as Usher syndrome. Low expression of this gene is associated with poor prognosis of colorectal cancer patients. [provided by RefSeq, Mar 2017]

CEP78 Gene-Disease associations (from GenCC):

• cone-rod dystrophy and hearing loss

  Inheritance: Unknown, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P
• cone-rod dystrophy and hearing loss 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Usher syndrome type 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28181368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330691.3. 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
	CEP78	NM_001330691.3	MANE Select	c.54C>G	p.His18Gln	missense	Exon 1 of 17	NP_001317620.1	Q5JTW2-3
	CEP78	NM_001098802.3		c.54C>G	p.His18Gln	missense	Exon 1 of 16	NP_001092272.1	Q5JTW2-2
	CEP78	NM_001349838.2		c.54C>G	p.His18Gln	missense	Exon 1 of 16	NP_001336767.1	A0A2R8YCP0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP78	ENST00000643273.2	MANE Select	c.54C>G	p.His18Gln	missense	Exon 1 of 17	ENSP00000496423.2	Q5JTW2-3
	CEP78	ENST00000376597.9	TSL:1	c.54C>G	p.His18Gln	missense	Exon 1 of 16	ENSP00000365782.4	Q5JTW2-2
	CEP78	ENST00000643499.1		c.54C>G	p.His18Gln	missense	Exon 1 of 17	ENSP00000495962.1	A0A2R8Y7A4

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.24
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.078
Sift	Benign	0.044	D
Sift4G	Benign	0.066	T
Polyphen		0.38	B
Vest4		0.16
MutPred		0.55		Gain of sheet (P = 0.0827)
MVP		0.32
MPC		0.11
ClinPred		0.74	D
GERP RS		3.2
PromoterAI		0.053	Neutral
Varity_R		0.45
gMVP		0.62
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2118041989; hg19: chr9-80851320;