rs1060502243
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_000093.5(COL5A1):c.1352A>T(p.Glu451Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E451K) has been classified as Likely benign.
Frequency
Consequence
NM_000093.5 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 |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.1352A>T | p.Glu451Val | missense_variant | 9/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.1352A>T | p.Glu451Val | missense_variant | 9/66 | ||
COL5A1 | XM_017014266.3 | c.1352A>T | p.Glu451Val | missense_variant | 9/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.1352A>T | p.Glu451Val | missense_variant | 9/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.1352A>T | p.Glu451Val | missense_variant | 9/66 | 2 | A2 | ||
COL5A1 | ENST00000469093.1 | n.91A>T | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2016 | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL5A1-related disease. 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"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This sequence change replaces glutamic acid with valine at codon 451 of the COL5A1 protein (p.Glu451Val). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at