rs200444162

Positions:

• chr5-37182833-G-A
• chr5-37182833-G-T

Variant summary

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

The NM_001384732.1(CPLANE1):​c.5348C>T​(p.Ala1783Val) variant causes a missense change involving the alteration of a conserved nucleotide. 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. A1783D) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPLANE1 NM_001384732.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.88

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 chr5-37182833-G-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPLANE1	NM_001384732.1	c.5348C>T	p.Ala1783Val	missense_variant	26/53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2	c.5348C>T	p.Ala1783Val	missense_variant	26/53		NM_001384732.1	ENSP00000498265	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T;T;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	.;T;T
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.016	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.75
MVP		0.48
MPC		0.57
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.26
gMVP		0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs200444162; hg19: chr5-37182935;