NM_001319944.2:c.602C>T

Variant names:

• chr1-26255564-C-T
• rs148974720
• NM_001319944.2:c.602C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319944.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85	NM_001319944.2	MANE Select	c.602C>T	p.Pro201Leu	missense	Exon 4 of 14	NP_001306873.1	Q6P2H3-2
	CEP85	NM_022778.5		c.602C>T	p.Pro201Leu	missense	Exon 4 of 14	NP_073615.2
	CEP85	NM_001281517.3		c.449C>T	p.Pro150Leu	missense	Exon 3 of 13	NP_001268446.1	Q6P2H3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85	ENST00000451429.8	TSL:2 MANE Select	c.602C>T	p.Pro201Leu	missense	Exon 4 of 14	ENSP00000417002.3	Q6P2H3-2
	CEP85	ENST00000252992.8	TSL:1	c.602C>T	p.Pro201Leu	missense	Exon 4 of 14	ENSP00000252992.4	Q6P2H3-1
	CEP85	ENST00000928442.1		c.602C>T	p.Pro201Leu	missense	Exon 4 of 14	ENSP00000598501.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.8
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	B
Vest4		0.51
MutPred		0.26		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
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs148974720; hg19: chr1-26582055;