chr5-37187488-G-C

Variant names:

• chr5-37187488-G-C
• rs367543061
• NM_001384732.1:c.4006C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM5

The NM_001384732.1(CPLANE1):​c.4006C>G​(p.Arg1336Gly) variant causes a missense change involving the alteration of a non-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. R1336Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPLANE1 NM_001384732.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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 chr5-37187488-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 31219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	NM_001384732.1	MANE Select	c.4006C>G	p.Arg1336Gly	missense	Exon 23 of 53	NP_001371661.1
	CPLANE1	NM_023073.4		c.4006C>G	p.Arg1336Gly	missense	Exon 23 of 52	NP_075561.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.4006C>G	p.Arg1336Gly	missense	Exon 23 of 53	ENSP00000498265.2
	CPLANE1	ENST00000514429.5	TSL:1	c.1150C>G	p.Arg384Gly	missense	Exon 8 of 37	ENSP00000424223.1
	CPLANE1	ENST00000509849.5	TSL:1	n.1021C>G		non_coding_transcript_exon	Exon 8 of 37	ENSP00000426337.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.86	T
PhyloP100		1.2
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.20
Sift	Uncertain	0.024	D
Sift4G	Pathogenic	0.0	D
Vest4		0.72
MVP		0.37
MPC		0.65
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.44
gMVP		0.44
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs367543061; hg19: chr5-37187590;