Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_014956.5(CEP164):c.32A>C(p.Gln11Pro) variant causes a missense change involving the alteration of a 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 (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

CEP164
NM_014956.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.35

Publications

5 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
nephronophthisis 15
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, G2P
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP164 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.764

PP5

Variant 11-117338618-A-C is Pathogenic according to our data. Variant chr11-117338618-A-C is described in ClinVar as Pathogenic. ClinVar VariationId is 37295.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP164	NM_014956.5	MANE Select	c.32A>C	p.Gln11Pro	missense	Exon 3 of 33	NP_055771.4
CEP164	NM_001440949.1		c.32A>C	p.Gln11Pro	missense	Exon 3 of 33	NP_001427878.1
CEP164	NM_001440950.1		c.32A>C	p.Gln11Pro	missense	Exon 3 of 33	NP_001427879.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP164	ENST00000278935.8	TSL:1 MANE Select	c.32A>C	p.Gln11Pro	missense	Exon 3 of 33	ENSP00000278935.3
CEP164	ENST00000533570.1	TSL:1	c.32A>C	p.Gln11Pro	missense	Exon 2 of 4	ENSP00000431302.1
CEP164	ENST00000527609.5	TSL:1	c.32A>C	p.Gln11Pro	missense	Exon 3 of 5	ENSP00000436351.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephronophthisis 15 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.086

MetaRNN

Pathogenic

0.76

MetaSVM

Uncertain

-0.033

MutationAssessor

Uncertain

2.6

PhyloP100

8.3

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.57

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.97

MutPred

0.33

Loss of sheet (P = 0.0315)

MVP

0.89

MPC

0.58

ClinPred

0.99

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.88

Mutation Taster

=45/55

disease causing (ClinVar)

(source)

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

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rs387907309

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over