NM_018140.4:c.50C>G

Variant names:

• chr5-612411-C-G
• NM_018140.4:c.50C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018140.4(CEP72):​c.50C>G​(p.Ala17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP72 NM_018140.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0350
• Publications: 0 publications found

Genes affected

CEP72 (HGNC:25547): (centrosomal protein 72) The product of this gene is a member of the leucine-rich-repeat (LRR) superfamily of proteins. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. [provided by RefSeq, Jul 2008]

CEP72-DT (HGNC:55563): (CEP72 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05710548).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018140.4. 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
	CEP72	NM_018140.4	MANE Select	c.50C>G	p.Ala17Gly	missense	Exon 1 of 12	NP_060610.2	Q9P209-1
	CEP72	NR_164122.1		n.72C>G		non_coding_transcript_exon	Exon 1 of 16
	CEP72-DT	NR_103444.1		n.-201G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP72	ENST00000264935.6	TSL:1 MANE Select	c.50C>G	p.Ala17Gly	missense	Exon 1 of 12	ENSP00000264935.5	Q9P209-1
	CEP72	ENST00000856935.1		c.50C>G	p.Ala17Gly	missense	Exon 1 of 13	ENSP00000526994.1
	CEP72	ENST00000919286.1		c.50C>G	p.Ala17Gly	missense	Exon 1 of 12	ENSP00000589345.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.73
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.035
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.012
Sift	Benign	0.12	T
Sift4G	Benign	0.085	T
Polyphen		0.0010	B
Vest4		0.091
MutPred		0.22		Loss of stability (P = 0.0158)
MVP		0.15
MPC		0.056
ClinPred		0.045	T
GERP RS		-0.91
PromoterAI		0.10	Neutral
Varity_R		0.090
gMVP		0.22
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

hg19: chr5-612526;