rs879255576

Positions:

• chr12-94308841-AGTT-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_016122.3(CEP83):​c.2075_2077delAAC​(p.Gln692del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000048 in 1,459,562 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CEP83 NM_016122.3 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.10

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_016122.3. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 12-94308841-AGTT-A is Pathogenic according to our data. Variant chr12-94308841-AGTT-A is described in ClinVar as [Pathogenic]. Clinvar id is 139543.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-94308841-AGTT-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP83	NM_016122.3	c.2075_2077delAAC	p.Gln692del	disruptive_inframe_deletion	17/17	ENST00000397809.10	NP_057206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP83	ENST00000397809.10	c.2075_2077delAAC	p.Gln692del	disruptive_inframe_deletion	17/17	1	NM_016122.3	ENSP00000380911.4
CEP83	ENST00000339839.9	c.2075_2077delAAC	p.Gln692del	disruptive_inframe_deletion	16/16	1		ENSP00000344655.5
CEP83	ENST00000552632.5	c.467_469delAAC	p.Gln156del	disruptive_inframe_deletion	4/5	3		ENSP00000447094.1
CEP83	ENST00000546783.1	n.529_531delAAC		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1459562 Hom.: 0 AF XY: 0.00000275 AC XY: 2 AN XY: 726210

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: 0.00000631

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephronophthisis 18 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 05, 2014

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs879255576; hg19: chr12-94702617;