5-37158257-C-T

Variant names:

• chr5-37158257-C-T
• NM_001384732.1:c.7779G>A
• CPLANE1 p.Trp2593*

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001384732.1(CPLANE1):​c.7779G>A​(p.Trp2593*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPLANE1 NM_001384732.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• 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, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Illumina
• 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: Pathogenic. The variant received 10 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

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.7779G>A	p.Trp2593*	stop_gained	Exon 39 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.7779G>A	p.Trp2593*	stop_gained	Exon 39 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.7779G>A	p.Trp2593*	stop_gained	Exon 39 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.4923G>A	p.Trp1641*	stop_gained	Exon 24 of 37	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.4791G>A		non_coding_transcript_exon	Exon 24 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	33
DANN	Benign	0.97
Eigen	Uncertain	0.29
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.20	N
PhyloP100		-0.023
Mutation Taster		=4/196	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
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.

Other links and lift over

hg19: chr5-37158359;