Variant 9-78236423-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001330691.3(CEP78):c.73C>G(p.Leu25Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L25P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEP78
NM_001330691.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.843

Variant links:

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 links:

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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=0.14496437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP78	NM_001330691.3 linkuse as main transcript	c.73C>G	p.Leu25Val	missense_variant	1/17	ENST00000643273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP78	ENST00000643273.2 linkuse as main transcript	c.73C>G	p.Leu25Val	missense_variant	1/17		NM_001330691.3	P4	Q5JTW2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1449062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719594

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.73C>G (p.L25V) alteration is located in exon 1 (coding exon 1) of the CEP78 gene. This alteration results from a C to G substitution at nucleotide position 73, causing the leucine (L) at amino acid position 25 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.051

T;.;.;.;.;.;.;.;.;T;.;.;.;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.85

D;D;T;T;T;T;D;.;D;D;D;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.14

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.;.;.;.;L;L;L;.;L;.;.;.

MutationTaster

Benign

0.98

N;N;N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.92

N;.;.;.;.;.;.;N;N;N;.;.;.;N

REVEL

Benign

0.045

Sift

Benign

0.30

T;.;.;.;.;.;.;T;T;T;.;.;.;T

Sift4G

Benign

0.38

T;.;.;.;.;.;.;T;T;T;.;.;.;T

Polyphen

0.28

B;.;.;.;.;.;.;.;P;.;.;.;.;.

Vest4

0.11

MutPred

0.54

Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);Gain of catalytic residue at L25 (P = 0.0168);

MVP

0.27

MPC

0.11

ClinPred

0.33

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.19

gMVP

0.44

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over