NM_001384732.1:c.6407delC

Variant names:

• chr5-37170095-TG-T
• rs367543064
• NM_001384732.1:c.6407delC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001384732.1(CPLANE1):​c.6407delC​(p.Pro2136HisfsTer31) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPLANE1 NM_001384732.1 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 1.83

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-37170095-TG-T is Pathogenic according to our data. Variant chr5-37170095-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 31221.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-37170095-TG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1	c.6407delC	p.Pro2136HisfsTer31	frameshift_variant	Exon 33 of 53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2	c.6407delC	p.Pro2136HisfsTer31	frameshift_variant	Exon 33 of 53		NM_001384732.1	ENSP00000498265.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Joubert syndrome 17 Pathogenic:1 Other:1

Apr 06, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs367543064; hg19: chr5-37170197;