rs774263225

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.96
Variant links:
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)

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ACMG classification

Classification made for transcript

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
CEP72NM_018140.4 linkc.16C>A p.Pro6Thr missense_variant Exon 1 of 12 ENST00000264935.6 NP_060610.2 Q9P209-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP72ENST00000264935.6 linkc.16C>A p.Pro6Thr missense_variant Exon 1 of 12 1 NM_018140.4 ENSP00000264935.5 Q9P209-1
CEP72-DTENST00000506629.1 linkn.-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
show subpopulations
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; API