rs756856188

Variant names:

• chr5-37244521-C-G
• rs756856188
• NM_001384732.1:c.424G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-37244521-C-G
• chr5-37244521-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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, ClinGen, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 Pathogenic/Likely_pathogenic. ClinVar VariationId is 217592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1	c.424G>C	p.Glu142Gln	missense_variant	Exon 5 of 53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2	c.424G>C	p.Glu142Gln	missense_variant	Exon 5 of 53		NM_001384732.1	ENSP00000498265.2
CPLANE1	ENST00000508244.5	c.424G>C	p.Glu142Gln	missense_variant	Exon 4 of 51	5		ENSP00000421690.1
CPLANE1	ENST00000425232.7	n.205G>C		non_coding_transcript_exon_variant	Exon 2 of 30	5		ENSP00000389014.3
CPLANE1	ENST00000675547.1	n.640+958G>C		intron_variant	Intron 2 of 14

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
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.67	T
PhyloP100		6.9
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
Mutation Taster		=180/120	polymorphism

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

Other links and lift over

dbSNP: rs756856188; hg19: chr5-37244623;