5-37245583-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_001384732.1(CPLANE1):c.233G>T(p.Gly78Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000734 in 1,362,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G78G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001384732.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPLANE1 | NM_001384732.1 | c.233G>T | p.Gly78Val | missense_variant | 4/53 | ENST00000651892.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPLANE1 | ENST00000651892.2 | c.233G>T | p.Gly78Val | missense_variant | 4/53 | NM_001384732.1 | A2 | ||
CPLANE1 | ENST00000508244.5 | c.233G>T | p.Gly78Val | missense_variant | 3/51 | 5 | P2 | ||
CPLANE1 | ENST00000675547.1 | n.536G>T | non_coding_transcript_exon_variant | 2/15 | |||||
CPLANE1 | ENST00000425232.7 | c.17G>T | p.Gly6Val | missense_variant, NMD_transcript_variant | 1/30 | 5 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD4 exome AF: 7.34e-7 AC: 1AN: 1362658Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 670230
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2020 | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt C5orf42 protein function. This variant has been observed in individual(s) with clinical features of Joubert syndrome (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 537708). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 78 of the C5orf42 protein (p.Gly78Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at