NM_016122.3:c.2099G>A

Variant names:

• chr12-94308820-C-T
• rs2136265331
• NM_016122.3:c.2099G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016122.3(CEP83):​c.2099G>A​(p.Gly700Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G700R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP83 NM_016122.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• nephronophthisis 18

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37105814).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016122.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP83	NM_016122.3	MANE Select	c.2099G>A	p.Gly700Glu	missense	Exon 17 of 17	NP_057206.2	Q9Y592-1
	CEP83	NM_001042399.2		c.2099G>A	p.Gly700Glu	missense	Exon 16 of 16	NP_001035858.1	Q9Y592-1
	CEP83	NM_001346457.2		c.2099G>A	p.Gly700Glu	missense	Exon 16 of 17	NP_001333386.1	Q9Y592-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP83	ENST00000397809.10	TSL:1 MANE Select	c.2099G>A	p.Gly700Glu	missense	Exon 17 of 17	ENSP00000380911.4	Q9Y592-1
	CEP83	ENST00000339839.9	TSL:1	c.2099G>A	p.Gly700Glu	missense	Exon 16 of 16	ENSP00000344655.5	Q9Y592-1
	CEP83	ENST00000914421.1		c.2039G>A	p.Gly680Glu	missense	Exon 16 of 16	ENSP00000584480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Nephronophthisis 18 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.85	T
PhyloP100		1.7
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Uncertain	0.020	D
Sift4G	Benign	0.13	T
Vest4		0.27
MVP		0.69
MPC		0.50
ClinPred		0.71	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.056
gMVP		0.19
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs2136265331; hg19: chr12-94702596;