12-94308821-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016122.3(CEP83):​c.2098G>C​(p.Gly700Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,606,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G700E) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000028 ( 0 hom. )

Consequence

CEP83
NM_016122.3 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27618158).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP83NM_016122.3 linkc.2098G>C p.Gly700Arg 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.2098G>C p.Gly700Arg missense_variant Exon 17 of 17 1 NM_016122.3 ENSP00000380911.4 Q9Y592-1
CEP83ENST00000339839.9 linkc.2098G>C p.Gly700Arg missense_variant Exon 16 of 16 1 ENSP00000344655.5 Q9Y592-1
CEP83ENST00000552632.5 linkc.490G>C p.Gly164Arg missense_variant Exon 4 of 5 3 ENSP00000447094.1 H0YHH5
CEP83ENST00000546783.1 linkn.*6G>C downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1454492
Hom.:
0
Cov.:
28
AF XY:
0.00000414
AC XY:
3
AN XY:
723964
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:
0.00000362
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
18
DANN
Uncertain
0.98
Eigen
Benign
0.12
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.58
T;.;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.28
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.071
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.32
T;T;T
Vest4
0.091, 0.10
MVP
0.63
MPC
0.48
ClinPred
0.72
D
GERP RS
5.8
Varity_R
0.043
gMVP
0.23

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: rs753799181; hg19: chr12-94702597; API