rs1475562485

Variant names:

• chr11-93667628-A-C
• rs1475562485
• NM_033395.2:c.130A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-93667628-A-C
• chr11-93667628-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033395.2(CEP295):​c.130A>C​(p.Ile44Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. I44V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CEP295 NM_033395.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.30
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33862185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP295	NM_033395.2	c.130A>C	p.Ile44Leu	missense_variant	Exon 3 of 30	ENST00000325212.11	NP_203753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11	c.130A>C	p.Ile44Leu	missense_variant	Exon 3 of 30	2	NM_033395.2	ENSP00000316681.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396292 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 688650

African (AFR) AF: 0.00 AC: 0 AN: 31304

American (AMR) AF: 0.00 AC: 0 AN: 34842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25032

East Asian (EAS) AF: 0.00 AC: 0 AN: 35680

South Asian (SAS) AF: 0.00 AC: 0 AN: 78546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1078030

Other (OTH) AF: 0.00 AC: 0 AN: 57884

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.0033
Eigen_PC	Benign	0.028
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
PhyloP100		7.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.20
Sift	Benign	0.067	T
Sift4G	Benign	0.49	T
Polyphen		0.73	P
Vest4		0.56
MutPred		0.30		Loss of MoRF binding (P = 0.134);
MVP		0.030
MPC		0.32
ClinPred		0.96	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.39
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1475562485; hg19: chr11-93400794;