Variant rs587777486 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_016122.3(CEP83):c.121C>T(p.Arg41Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CEP83
NM_016122.3 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.223

Variant links:

Genes affected

CEP83 (HGNC:17966): (centrosomal protein 83) The protein encoded by this gene is a centriolar protein involved in primary cilium assembly. Defects in this gene have been associated with infantile nephronophthisis and intellectual disability. [provided by RefSeq, Oct 2016]

CEP83 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 12-94412370-G-A is Pathogenic according to our data. Variant chr12-94412370-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 139540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-94412370-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP83	NM_016122.3 linkuse as main transcript	c.121C>T	p.Arg41Ter	stop_gained	3/17	ENST00000397809.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP83	ENST00000397809.10 linkuse as main transcript	c.121C>T	p.Arg41Ter	stop_gained	3/17	1	NM_016122.3	P1	Q9Y592-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248342

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1460296

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephronophthisis 18

Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Invitae	Aug 27, 2022	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 139540). This premature translational stop signal has been observed in individual(s) with CEP83-related conditions (PMID: 24882706). This variant is present in population databases (rs587777486, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg41*) in the CEP83 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP83 are known to be pathogenic (PMID: 23530209, 24882706). -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jun 05, 2014	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.57

BayesDel_noAF

Pathogenic

0.50

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.60

MutationTaster

Benign

1.0

A;A;A;A

Vest4

0.49

GERP RS

1.5

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