CPLANE1 p.Val306Leu

Variant names:

• chr5-37238879-C-A
• NM_001384732.1:c.916G>T
• CPLANE1 p.Val306Leu

Your query was ambiguous. Multiple possible variants found:

• chr5-37238879-C-A
• chr5-37238879-C-G
• chr5-37238877-CAC-TAA
• chr5-37238877-CAC-AAG
• chr5-37238877-CAC-GAG
• chr5-37238877-CAC-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384732.1(CPLANE1):​c.916G>T​(p.Val306Leu) 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. 14/20 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. V306M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CPLANE1 NM_001384732.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503
• Publications: 0 publications found

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

ACMG classification

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=0.15042835).

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.916G>T	p.Val306Leu	missense	Exon 8 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.916G>T	p.Val306Leu	missense	Exon 8 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.916G>T	p.Val306Leu	missense	Exon 8 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000955438.1		c.916G>T	p.Val306Leu	missense	Exon 8 of 53	ENSP00000625497.1
	CPLANE1	ENST00000508244.5	TSL:5	c.916G>T	p.Val306Leu	missense	Exon 7 of 51	ENSP00000421690.1	Q9H799-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.50
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.045
Sift	Benign	0.081	T
Sift4G	Benign	0.076	T
Varity_R		0.061
gMVP		0.069
Mutation Taster		=89/11	polymorphism

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

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

Other links and lift over

hg19: chr5-37238981;