1-26255564-C-T

Variant names:

• chr1-26255564-C-T
• NM_001319944.2:c.602C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001319944.2(CEP85):​c.602C>T​(p.Pro201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. P201R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CEP85 NM_001319944.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

Genes affected

CEP85 (HGNC:25309): (centrosomal protein 85) This gene encodes a protein that belongs to the centrosome-associated family of proteins. The centrosome is a subcellular organelle in the animal cell that functions as a microtubule organizing center and is involved in cell-cycle progression. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115112334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85	NM_001319944.2	c.602C>T	p.Pro201Leu	missense_variant	Exon 4 of 14	ENST00000451429.8	NP_001306873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85	ENST00000451429.8	c.602C>T	p.Pro201Leu	missense_variant	Exon 4 of 14	2	NM_001319944.2	ENSP00000417002.3
CEP85	ENST00000252992.8	c.602C>T	p.Pro201Leu	missense_variant	Exon 4 of 14	1		ENSP00000252992.4
CEP85	ENST00000640292.2	c.449C>T	p.Pro150Leu	missense_variant	Exon 3 of 13	5		ENSP00000492362.2
CEP85	ENST00000480446.1	n.*214C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.036	.;.;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.0	.;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	.;.;N
REVEL	Benign	0.077
Sift	Benign	0.030	.;.;D
Sift4G	Benign	0.76	.;.;T
Polyphen		0.43, 0.045	.;B;B
Vest4		0.51
MutPred		0.26		.;Loss of disorder (P = 0.0464);Loss of disorder (P = 0.0464);
MVP		0.40
MPC		0.42
ClinPred		0.48	T
GERP RS		5.4
Varity_R		0.058
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-26582055;