Variant 12-94308883-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_016122.3(CEP83):c.2036G>A(p.Arg679His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,611,990 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R679C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

CEP83
NM_016122.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.44

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009636164).

BP6

Variant 12-94308883-C-T is Benign according to our data. Variant chr12-94308883-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2193609.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP83	NM_016122.3 linkuse as main transcript	c.2036G>A	p.Arg679His	missense_variant	17/17	ENST00000397809.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP83	ENST00000397809.10 linkuse as main transcript	c.2036G>A	p.Arg679His	missense_variant	17/17	1	NM_016122.3	P1	Q9Y592-1
CEP83	ENST00000339839.9 linkuse as main transcript	c.2036G>A	p.Arg679His	missense_variant	16/16	1		P1	Q9Y592-1
CEP83	ENST00000552632.5 linkuse as main transcript	c.428G>A	p.Arg143His	missense_variant	4/5	3
CEP83	ENST00000546783.1 linkuse as main transcript	n.490G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152102

Hom.:

Cov.:

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:

0.000207

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000329

AC:

AN:

248958

Hom.:

AF XY:

0.000341

AC XY:

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00344

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000146

AC:

213

AN:

1459770

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

106

AN XY:

726278

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:

0.00378

Gnomad4 NFE exome

AF:

0.00000721

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000296

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74418

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:

0.000207

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000270

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000364

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephronophthisis 18

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 11, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.15

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.021

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

T;.;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0096

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.7

D;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.022

D;D;D

Sift4G

Uncertain

0.019

D;T;T

Vest4

0.14, 0.15

MVP

0.59

MPC

0.10

ClinPred

0.13

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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