rs567435284
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_004928.3(CFAP410):āc.269G>Cā(p.Arg90Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,786 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R90Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_004928.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFAP410 | NM_004928.3 | c.269G>C | p.Arg90Pro | missense_variant | 4/7 | ENST00000339818.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFAP410 | ENST00000339818.9 | c.269G>C | p.Arg90Pro | missense_variant | 4/7 | 1 | NM_004928.3 | P4 | |
ENST00000448927.1 | n.1705-65C>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459786Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726156
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 08, 2023 | This missense change has been observed in individual(s) with cone-rod dystrophy (PMID: 28041643). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 CFAP410 protein function. ClinVar contains an entry for this variant (Variation ID: 438158). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 90 of the CFAP410 protein (p.Arg90Pro). - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 14, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32581362, 28041643) - |
Retinal dystrophy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at