Genetic Variant CPLANE1:p.Pro1436Ala (chr5-37184963-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384732.1(CPLANE1):c.4306C>G(p.Pro1436Ala) 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. 12/20 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. P1436S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CPLANE1
NM_001384732.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.09

Publications

2 publications found

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]

CPLANE1 Gene-Disease associations (from GenCC):

Joubert syndrome 17
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, G2P, Illumina, Labcorp Genetics (formerly Invitae)
orofaciodigital syndrome type 6
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CPLANE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18541753).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384732.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	NM_001384732.1	MANE Select	c.4306C>G	p.Pro1436Ala	missense	Exon 25 of 53	NP_001371661.1
	CPLANE1	NM_023073.4		c.4306C>G	p.Pro1436Ala	missense	Exon 25 of 52	NP_075561.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CPLANE1	ENST00000651892.2	MANE Select	c.4306C>G	p.Pro1436Ala	missense	Exon 25 of 53	ENSP00000498265.2
CPLANE1	ENST00000514429.5	TSL:1	c.1450C>G	p.Pro484Ala	missense	Exon 10 of 37	ENSP00000424223.1
CPLANE1	ENST00000509849.5	TSL:1	n.1321C>G		non_coding_transcript_exon	Exon 10 of 37	ENSP00000426337.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251434

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

0.0019

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.67

M_CAP

Benign

0.040

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.52

PhyloP100

3.1

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.20

Sift

Uncertain

0.012

Sift4G

Uncertain

0.040

Vest4

0.36

MVP

0.66

MPC

0.50

ClinPred

0.95

GERP RS

5.2

Varity_R

0.11

gMVP

0.10

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over