5-612368-C-G

Position:

• chr5-612368-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018140.4(CEP72):​c.7C>G​(p.Arg3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,336,892 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CEP72 NM_018140.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.333

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060558856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP72	NM_018140.4	c.7C>G	p.Arg3Gly	missense_variant	1/12	ENST00000264935.6	NP_060610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP72	ENST00000264935.6	c.7C>G	p.Arg3Gly	missense_variant	1/12	1	NM_018140.4	ENSP00000264935	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.48e-7 AC: 1 AN: 1336892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 659386

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: 9.46e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.7C>G (p.R3G) alteration is located in exon 1 (coding exon 1) of the CEP72 gene. This alteration results from a C to G substitution at nucleotide position 7, causing the arginine (R) at amino acid position 3 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.77
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.043
Sift	Benign	0.32	T
Sift4G	Benign	0.33	T
Polyphen		0.016	B
Vest4		0.11
MutPred		0.45		Loss of MoRF binding (P = 2e-04);
MVP		0.20
MPC		0.079
ClinPred		0.081	T
GERP RS		0.95
Varity_R		0.12
gMVP		0.27

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-612483;