11-93683641-C-A

Position:

• chr11-93683641-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033395.2(CEP295):​c.848C>A​(p.Pro283Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP295 NM_033395.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.60

Genes affected

CEP295 (HGNC:29366): (centrosomal protein 295) Enables microtubule binding activity. Involved in several processes, including centriole replication; positive regulation of protein acetylation; and regulation of centrosome duplication. Located in cytosol; microtubule cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP295	NM_033395.2	c.848C>A	p.Pro283Gln	missense_variant	8/30	ENST00000325212.11	NP_203753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11	c.848C>A	p.Pro283Gln	missense_variant	8/30	2	NM_033395.2	ENSP00000316681.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.848C>A (p.P283Q) alteration is located in exon 8 (coding exon 7) of the CEP295 gene. This alteration results from a C to A substitution at nucleotide position 848, causing the proline (P) at amino acid position 283 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.81	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.063	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.32		Loss of catalytic residue at P283 (P = 0.0211);
MVP		0.11
MPC		0.44
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.33
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-93416807;