rs774263225

Variant names:

• chr5-612377-C-A
• NM_018140.4:c.16C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-612377-C-A
• chr5-612377-C-G
• chr5-612377-C-T

Variant summary

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

The NM_018140.4(CEP72):​c.16C>A​(p.Pro6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,339,092 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. P6S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CEP72 NM_018140.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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

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=0.03866148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP72	NM_018140.4	c.16C>A	p.Pro6Thr	missense_variant	Exon 1 of 12	ENST00000264935.6	NP_060610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP72	ENST00000264935.6	c.16C>A	p.Pro6Thr	missense_variant	Exon 1 of 12	1	NM_018140.4	ENSP00000264935.5
CEP72-DT	ENST00000506629.1	n.-167G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.47e-7 AC: 1 AN: 1339092 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 660436

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: 9.45e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.47
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.11
Sift	Benign	0.93	T
Sift4G	Benign	0.53	T
Polyphen		0.0060	B
Vest4		0.066
MutPred		0.34		Gain of MoRF binding (P = 0.0597);
MVP		0.099
MPC		0.064
ClinPred		0.040	T
GERP RS		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.045
gMVP		0.24

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: chr5-612492;