rs116198390

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001384732.1(CPLANE1):c.9016A>G(p.Arg3006Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000369 in 1,613,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

CPLANE1
NM_001384732.1 missense, splice_region

Scores

Splicing: ADA: 0.9929

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: 4.04

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

CPLANE1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001384732.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	NM_001384732.1	MANE Select	c.9016A>G	p.Arg3006Gly	missense splice_region	Exon 48 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.8854A>G	p.Arg2952Gly	missense splice_region	Exon 47 of 52	NP_075561.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPLANE1	ENST00000651892.2	MANE Select	c.9016A>G	p.Arg3006Gly	missense splice_region	Exon 48 of 53	ENSP00000498265.2	A0A494BZW6
CPLANE1	ENST00000514429.5	TSL:1	c.6052A>G	p.Arg2018Gly	missense splice_region	Exon 32 of 37	ENSP00000424223.1	H0Y9I8
CPLANE1	ENST00000509849.5	TSL:1	n.*358A>G		splice_region non_coding_transcript_exon	Exon 32 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000327

AC:

AN:

250452

AF XY:

0.000295

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000584

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000626

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000372

AC:

543

AN:

1460738

Hom.:

Cov.:

AF XY:

0.000356

AC XY:

259

AN XY:

726702

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33444

American (AMR)

AF:

0.0000898

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

86046

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000454

AC:

505

AN:

1111416

Other (OTH)

AF:

0.000232

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000348

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41586

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000461

Hom.:

Bravo

AF:

0.000223

EpiCase

AF:

0.000546

EpiControl

AF:

0.000297

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Inborn genetic diseases (1)

Joubert syndrome 17 (1)

Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.82

M_CAP

Benign

0.020

MetaRNN

Benign

0.11

MetaSVM

Uncertain

-0.0047

PhyloP100

4.0

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.28

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Varity_R

0.56

gMVP

0.16

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.90

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over