5-37224655-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001384732.1(CPLANE1):​c.2377C>G​(p.Gln793Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

CPLANE1
NM_001384732.1 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36
Variant links:
Genes affected
CPLANE1 (HGNC:25801): (ciliogenesis and planar polarity effector complex subunit 1) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. Defects in this gene are a cause of Joubert syndrome (JBTS). [provided by RefSeq, May 2012]

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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=0.05047238).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPLANE1NM_001384732.1 linkc.2377C>G p.Gln793Glu missense_variant Exon 13 of 53 ENST00000651892.2 NP_001371661.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPLANE1ENST00000651892.2 linkc.2377C>G p.Gln793Glu missense_variant Exon 13 of 53 NM_001384732.1 ENSP00000498265.2 A0A494BZW6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399090
Hom.:
0
Cov.:
31
AF XY:
0.00000145
AC XY:
1
AN XY:
690062
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:
0.00
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
8.9
DANN
Benign
0.17
DEOGEN2
Benign
0.0070
T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.083
N
LIST_S2
Benign
0.60
.;T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-0.94
T
PROVEAN
Benign
-0.58
N;N
REVEL
Benign
0.026
Sift
Benign
0.57
T;T
Sift4G
Benign
0.098
T;T
Vest4
0.091
MutPred
0.13
Gain of phosphorylation at S792 (P = 0.1265);Gain of phosphorylation at S792 (P = 0.1265);
MVP
0.22
MPC
0.13
ClinPred
0.037
T
GERP RS
2.5
Varity_R
0.049
gMVP
0.034

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr5-37224757; API