chr1-26244252-C-T

Variant names:

• chr1-26244252-C-T
• rs560353875
• NM_001319944.2:c.142C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001319944.2(CEP85):​c.142C>T​(p.Arg48Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R48H) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: CEP85 NM_001319944.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21895519).

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.142C>T	p.Arg48Cys	missense	Exon 3 of 14	NP_001306873.1	Q6P2H3-2
	CEP85	NM_022778.5		c.142C>T	p.Arg48Cys	missense	Exon 3 of 14	NP_073615.2
	CEP85	NM_001281517.3		c.55+4414C>T		intron	N/A	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.142C>T	p.Arg48Cys	missense	Exon 3 of 14	ENSP00000417002.3	Q6P2H3-2
	CEP85	ENST00000252992.8	TSL:1	c.142C>T	p.Arg48Cys	missense	Exon 3 of 14	ENSP00000252992.4	Q6P2H3-1
	CEP85	ENST00000928442.1		c.142C>T	p.Arg48Cys	missense	Exon 3 of 14	ENSP00000598501.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151990 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000636 AC: 16 AN: 251424 AF XY: 0.0000883

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000472 AC: 69 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45 AN XY: 727186

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

American (AMR) AF: 0.00 AC: 0 AN: 44718

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.000510 AC: 44 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111922

Other (OTH) AF: 0.000116 AC: 7 AN: 60382

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152108 Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41480

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.33		Gain of helix (P = 0.0022)
MVP		0.59
MPC		0.49
ClinPred		0.85	D
GERP RS		4.9
Varity_R		0.44
gMVP		0.48
Mutation Taster		=83/17	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: rs560353875; hg19: chr1-26570743; COSMIC: COSV104581557;