12-94308899-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016122.3(CEP83):​c.2020G>A​(p.Glu674Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CEP83
NM_016122.3 missense

Scores

6
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP83NM_016122.3 linkc.2020G>A p.Glu674Lys missense_variant Exon 17 of 17 ENST00000397809.10 NP_057206.2 Q9Y592-1Q3B787

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP83ENST00000397809.10 linkc.2020G>A p.Glu674Lys missense_variant Exon 17 of 17 1 NM_016122.3 ENSP00000380911.4 Q9Y592-1
CEP83ENST00000339839.9 linkc.2020G>A p.Glu674Lys missense_variant Exon 16 of 16 1 ENSP00000344655.5 Q9Y592-1
CEP83ENST00000552632.5 linkc.412G>A p.Glu138Lys missense_variant Exon 4 of 5 3 ENSP00000447094.1 H0YHH5
CEP83ENST00000546783.1 linkn.474G>A non_coding_transcript_exon_variant Exon 3 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458538
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
725758
show subpopulations
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Nephronophthisis 18 Uncertain:1
Mar 02, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 674 of the CEP83 protein (p.Glu674Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CEP83-related conditions. ClinVar contains an entry for this variant (Variation ID: 954930). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.79
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
29
DANN
Uncertain
1.0
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.92
D;.;D
M_CAP
Benign
0.060
D
MetaRNN
Uncertain
0.53
D;D;D
MetaSVM
Benign
-0.46
T
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-2.0
N;N;N
REVEL
Benign
0.26
Sift
Uncertain
0.0060
D;D;D
Sift4G
Pathogenic
0.0
D;T;T
Vest4
0.56, 0.56
MVP
0.78
MPC
0.47
ClinPred
0.92
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.56

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.

Other links and lift over

dbSNP: rs1969381470; hg19: chr12-94702675; API