rs387907311

Positions:

• chr11-117381864-C-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_014956.5(CEP164):​c.1573C>T​(p.Gln525*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CEP164 NM_014956.5 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 0.380

Genes affected

CEP164 (HGNC:29182): (centrosomal protein 164) This gene encodes a centrosomal protein involved in microtubule organization, DNA damage response, and chromosome segregation. The encoded protein is required for assembly of primary cilia and localizes to mature centrioles. Defects in this gene are a cause of nephronophthisis-related ciliopathies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

CEP164 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-117381864-C-T is Pathogenic according to our data. Variant chr11-117381864-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 37297.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP164	NM_014956.5	c.1573C>T	p.Gln525*	stop_gained	13/33	ENST00000278935.8	NP_055771.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP164	ENST00000278935.8	c.1573C>T	p.Gln525*	stop_gained	13/33	1	NM_014956.5	ENSP00000278935.3
CEP164	ENST00000533675.5	n.1828C>T		non_coding_transcript_exon_variant	9/27	2
CEP164	ENST00000533706.5	n.897C>T		non_coding_transcript_exon_variant	6/27	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Nephronophthisis 15 Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Aug 03, 2012	- -
Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 20, 2022	ClinVar contains an entry for this variant (Variation ID: 37297). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with nephronophthisis-related ciliopathies (PMID: 22863007). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln525*) in the CEP164 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP164 are known to be pathogenic (PMID: 22863007, 28125082, 32367404, 34132027, 34499853). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	34
DANN	Uncertain	1.0
Eigen	Benign	0.13
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.072	N
Vest4		0.12
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs387907311; hg19: chr11-117252580;