dbSNP rs1057519066: CPLANE1:p.Met694Val (chr5-37226515-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384732.1(CPLANE1):c.2080A>G(p.Met694Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M694I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CPLANE1
NM_001384732.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

Publications

0 publications found

Variant links:

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

CPLANE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.2572193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPLANE1	NM_001384732.1 link	c.2080A>G	p.Met694Val	missense_variant	Exon 12 of 53	ENST00000651892.2	NP_001371661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPLANE1	ENST00000651892.2 link	c.2080A>G	p.Met694Val	missense_variant	Exon 12 of 53		NM_001384732.1	ENSP00000498265.2		A0A494BZW6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000652

AC:

AN:

153318

AF XY:

0.0000123

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000926

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1396160

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31350

American (AMR)

AF:

0.00

AC:

AN:

34998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25046

East Asian (EAS)

AF:

0.0000281

AC:

AN:

35650

South Asian (SAS)

AF:

0.00

AC:

AN:

78412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077964

Other (OTH)

AF:

0.00

AC:

AN:

57826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

0.0080

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.036

T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.63

.;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.26

T;T

MetaSVM

Pathogenic

0.94

PhyloP100

2.5

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.45

Sift

Benign

0.11

T;T

Sift4G

Benign

0.097

T;T

Vest4

0.23

MutPred

0.40

Loss of ubiquitination at K693 (P = 0.1372);Loss of ubiquitination at K693 (P = 0.1372);

MVP

0.66

MPC

0.29

ClinPred

0.30

GERP RS

5.2

Varity_R

0.23

gMVP

0.19

Mutation Taster

=85/15

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over