9-78236391-ACTT-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2 PM4_Supporting BP6_Moderate BS1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.52

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]

ACMG classification

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	UniProt
CEP78	NM_001330691.3	c.47_49del	p.Phe16del	inframe_deletion	1/17	ENST00000643273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP78	ENST00000643273.2	c.47_49del	p.Phe16del	inframe_deletion	1/17		NM_001330691.3	P4

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152038 Hom.: 0 Cov.: 33

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.: 0 AF XY: 0.000444 AC XY: 51 AN XY: 114896

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.: 1 AF XY: 0.000208 AC XY: 149 AN XY: 715146

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: 23 AN: 152156 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74378

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.: 0

Bravo AF: 0.000223

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs765143446; hg19: chr9-80851307;