rs756856188

chr5-37244521-C-Gchr5-37244521-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_001384732.1(CPLANE1):c.424G>C(p.Glu142Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. E142K) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CPLANE1 NM_001384732.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.93

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr5-37244521-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 217592.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=3, Pathogenic=3, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLANE1	NM_001384732.1	c.424G>C	p.Glu142Gln	missense_variant	5/53	ENST00000651892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLANE1	ENST00000651892.2	c.424G>C	p.Glu142Gln	missense_variant	5/53		NM_001384732.1	A2
CPLANE1	ENST00000508244.5	c.424G>C	p.Glu142Gln	missense_variant	4/51	5		P2
CPLANE1	ENST00000425232.7	c.208G>C	p.Glu70Gln	missense_variant, NMD_transcript_variant	2/30	5
CPLANE1	ENST00000675547.1	n.640+958G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.043	T;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.67	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.18
Sift	Benign	0.10	T;T
Sift4G	Pathogenic	0.0	D;D
Vest4		0.70
MutPred		0.37		Loss of catalytic residue at E142 (P = 0.0688);Loss of catalytic residue at E142 (P = 0.0688);
MVP		0.76
MPC		0.57
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.25
gMVP		0.34

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-37244623;