9-78236434-G-C

Position:

• chr9-78236434-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001330691.3(CEP78):​c.84G>C​(p.Ser28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,599,716 control chromosomes in the GnomAD database, including 109,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8446 hom., cov: 32)
  • Exomes 𝑓: 0.37 (101240 hom.)
• Consequence: CEP78 NM_001330691.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.102

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 9-78236434-G-C is Benign according to our data. Variant chr9-78236434-G-C is described in ClinVar as [Benign]. Clinvar id is 517538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.102 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP78	NM_001330691.3	c.84G>C	p.Ser28=	synonymous_variant	1/17	ENST00000643273.2	NP_001317620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP78	ENST00000643273.2	c.84G>C	p.Ser28=	synonymous_variant	1/17		NM_001330691.3	ENSP00000496423	P4

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48386 AN: 151974 Hom.: 8445 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.342

GnomAD3 exomes AF: 0.350 AC: 77528 AN: 221520 Hom.: 13869 AF XY: 0.357 AC XY: 43131 AN XY: 120828

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.268

Gnomad SAS exome AF: 0.381

Gnomad FIN exome AF: 0.368

Gnomad NFE exome AF: 0.384

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.371 AC: 537296 AN: 1447624 Hom.: 101240 Cov.: 42 AF XY: 0.373 AC XY: 267954 AN XY: 718684

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.318 AC: 48410 AN: 152092 Hom.: 8446 Cov.: 32 AF XY: 0.319 AC XY: 23688 AN XY: 74344

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.340

Alfa AF: 0.344 Hom.: 3015

Bravo AF: 0.308

Asia WGS AF: 0.291 AC: 1015 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.Ser28Ser in exon 1 of CEP78: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 45.32% (19356/42712) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs10867166). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.6
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs10867166; hg19: chr9-80851350; COSMIC: COSV52846118;