chr5-37125255-T-C

Variant names:

• chr5-37125255-T-C
• rs1345413118
• NM_001384732.1:c.8947A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384732.1(CPLANE1):​c.8947A>G​(p.Arg2983Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPLANE1 NM_001384732.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2169841).

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.8947A>G	p.Arg2983Gly	missense	Exon 47 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.8785A>G	p.Arg2929Gly	missense	Exon 46 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.8947A>G	p.Arg2983Gly	missense	Exon 47 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.5983A>G	p.Arg1995Gly	missense	Exon 31 of 37	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.*289A>G		non_coding_transcript_exon	Exon 31 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.78	T
PhyloP100		0.62
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.22
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.010	D
Vest4		0.45
MVP		0.51
MPC		0.17
ClinPred		0.94	D
GERP RS		3.6
Varity_R		0.16
gMVP		0.10
Mutation Taster		=91/9	polymorphism

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: rs1345413118; hg19: chr5-37125357;