rs1554787531
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_000093.5(COL5A1):āc.668A>Gā(p.Gln223Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,738 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 ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q223P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000093.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.668A>G | p.Gln223Arg | missense_variant | 5/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.668A>G | p.Gln223Arg | missense_variant | 5/66 | ||
COL5A1 | XM_017014266.3 | c.668A>G | p.Gln223Arg | missense_variant | 5/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.668A>G | p.Gln223Arg | missense_variant | 5/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.668A>G | p.Gln223Arg | missense_variant | 5/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461738Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727180
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 23, 2017 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with COL5A1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with arginine at codon 223 of the COL5A1 protein (p.Gln223Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at