11-117351872-C-G

Variant names:

• chr11-117351872-C-G
• rs387907310
• NM_014956.5:c.277C>G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM5 PP3

The NM_014956.5(CEP164):​c.277C>G​(p.Arg93Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R93Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP164 NM_014956.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.84
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr11-117351872-C-T is described in CliVar as Likely_pathogenic. Clinvar id is 37296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP164	NM_014956.5	c.277C>G	p.Arg93Gly	missense_variant	Exon 5 of 33	ENST00000278935.8	NP_055771.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP164	ENST00000278935.8	c.277C>G	p.Arg93Gly	missense_variant	Exon 5 of 33	1	NM_014956.5	ENSP00000278935.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	.;T;T;T;.;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D;.;D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Pathogenic	3.0	.;.;M;.;.;.
PhyloP100		3.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-7.0	D;D;D;D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D
Polyphen		1.0	.;.;D;.;.;.
Vest4		0.79
MutPred		0.59		Loss of helix (P = 0.0093);.;Loss of helix (P = 0.0093);.;Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.95
MPC		0.59
ClinPred		0.99	D
GERP RS		6.0
PromoterAI		-0.038	Neutral
Varity_R		0.72
gMVP		0.58
Mutation Taster		=55/45	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: rs387907310; hg19: chr11-117222588;