Variant 9-78236391-ACTT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PM4_SupportingBP6_ModerateBS1

The NM_001330691.3(CEP78):c.47_49del(p.Phe16del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000212 in 1,593,102 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

CEP78
NM_001330691.3 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.52

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001330691.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 9-78236391-ACTT-A is Benign according to our data. Variant chr9-78236391-ACTT-A is described in ClinVar as [Likely_benign]. Clinvar id is 1105283.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000219 (315/1440946) while in subpopulation AMR AF= 0.00182 (77/42374). AF 95% confidence interval is 0.00149. There are 1 homozygotes in gnomad4_exome. There are 149 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP78	NM_001330691.3 linkuse as main transcript	c.47_49del	p.Phe16del	inframe_deletion	1/17	ENST00000643273.2	NP_001317620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP78	ENST00000643273.2 linkuse as main transcript	c.47_49del	p.Phe16del	inframe_deletion	1/17		NM_001330691.3	ENSP00000496423	P4	Q5JTW2-3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000487

AC:

102

AN:

209516

Hom.:

AF XY:

0.000444

AC XY:

AN XY:

114896

show subpopulations

Gnomad AFR exome

AF:

0.0000872

Gnomad AMR exome

AF:

0.00206

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000638

Gnomad SAS exome

AF:

0.000256

Gnomad FIN exome

AF:

0.0000583

Gnomad NFE exome

AF:

0.000272

Gnomad OTH exome

AF:

0.000375

GnomAD4 exome

AF:

0.000219

AC:

315

AN:

1440946

Hom.:

AF XY:

0.000208

AC XY:

149

AN XY:

715146

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.0000775

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.000151

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000223

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over