rs1969381470

Variant names:

• chr12-94308899-C-T
• rs1969381470
• NM_016122.3:c.2020G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2020G>A	p.Glu674Lys	missense	Exon 17 of 17	NP_057206.2	Q9Y592-1
	CEP83	NM_001042399.2		c.2020G>A	p.Glu674Lys	missense	Exon 16 of 16	NP_001035858.1	Q9Y592-1
	CEP83	NM_001346457.2		c.2020G>A	p.Glu674Lys	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.2020G>A	p.Glu674Lys	missense	Exon 17 of 17	ENSP00000380911.4	Q9Y592-1
	CEP83	ENST00000339839.9	TSL:1	c.2020G>A	p.Glu674Lys	missense	Exon 16 of 16	ENSP00000344655.5	Q9Y592-1
	CEP83	ENST00000914421.1		c.1960G>A	p.Glu654Lys	missense	Exon 16 of 16	ENSP00000584480.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109238

Other (OTH) AF: 0.00 AC: 0 AN: 60242

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	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
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.46	T
PhyloP100		4.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.26
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Vest4		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
Mutation Taster		=78/22	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: rs1969381470; hg19: chr12-94702675;