5-37153973-G-C

Variant names:

• chr5-37153973-G-C
• rs147416429
• NM_001384732.1:c.8140C>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.8140C>G​(p.Arg2714Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2714Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CPLANE1 NM_001384732.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1411559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1	c.8140C>G	p.Arg2714Gly	missense_variant	Exon 42 of 53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2	c.8140C>G	p.Arg2714Gly	missense_variant	Exon 42 of 53		NM_001384732.1	ENSP00000498265.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458048 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724700

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.00 AC: 0 AN: 85736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109460

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.0	.;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	.;.;.
PhyloP100		3.7
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.029	D;D;D
Sift4G	Uncertain	0.033	D;D;D
Vest4		0.17
ClinPred		0.30	T
GERP RS		5.2
Varity_R		0.13
gMVP		0.099
Mutation Taster		=85/15	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: rs147416429; hg19: chr5-37154075;