rs778892188
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001853.4(COL9A3):c.1747C>T(p.Arg583Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,450 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R583H) has been classified as Likely benign.
Frequency
Consequence
NM_001853.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL9A3 | NM_001853.4 | c.1747C>T | p.Arg583Cys | missense_variant | 30/32 | ENST00000649368.1 | |
COL9A3 | XM_047439893.1 | c.1924C>T | p.Arg642Cys | missense_variant | 29/31 | ||
COL9A3 | XM_047439894.1 | c.1186C>T | p.Arg396Cys | missense_variant | 30/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL9A3 | ENST00000649368.1 | c.1747C>T | p.Arg583Cys | missense_variant | 30/32 | NM_001853.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246282Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134232
GnomAD4 exome AF: 0.00000891 AC: 13AN: 1459450Hom.: 0 Cov.: 35 AF XY: 0.00000826 AC XY: 6AN XY: 726150
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Bilateral sensorineural hearing impairment Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center of Genomic medicine, Geneva, University Hospital of Geneva | Feb 09, 2016 | - - |
Intervertebral disc disorder;C1832998:Epiphyseal dysplasia, multiple, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 08, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 583 of the COL9A3 protein (p.Arg583Cys). This variant is present in population databases (rs778892188, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL9A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 375457). 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 not expected to disrupt COL9A3 protein function with a negative predictive value of 95%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at