NM_001384732.1:c.7778G>C

Variant names:

• chr5-37158258-C-G
• rs863225159
• NM_001384732.1:c.7778G>C

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.7778G>C​(p.Trp2593Ser) 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. 14/20 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: 0.488
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08472642).

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.7778G>C	p.Trp2593Ser	missense	Exon 39 of 53	NP_001371661.1
	CPLANE1	NM_023073.4		c.7778G>C	p.Trp2593Ser	missense	Exon 39 of 52	NP_075561.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.7778G>C	p.Trp2593Ser	missense	Exon 39 of 53	ENSP00000498265.2
	CPLANE1	ENST00000514429.5	TSL:1	c.4922G>C	p.Trp1641Ser	missense	Exon 24 of 37	ENSP00000424223.1
	CPLANE1	ENST00000509849.5	TSL:1	n.4790G>C		non_coding_transcript_exon	Exon 24 of 37	ENSP00000426337.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.7
DANN	Benign	0.74
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.49
PROVEAN	Benign	1.5	N
REVEL	Benign	0.041
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Vest4		0.10
MVP		0.076
MPC		0.20
ClinPred		0.088	T
GERP RS		2.4
Varity_R		0.15
gMVP		0.20
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs863225159; hg19: chr5-37158360;