chr9-134842283-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_000093.5(COL5A1):c.5497C>T(p.Pro1833Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,074 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 (★). Synonymous variant affecting the same amino acid position (i.e. P1833P) has been classified as Likely benign.
Frequency
Consequence
NM_000093.5 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 |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.5497C>T | p.Pro1833Ser | missense_variant | 66/66 | ENST00000371817.8 | |
LOC101448202 | NR_103451.2 | n.71-22074G>A | intron_variant, non_coding_transcript_variant | ||||
COL5A1 | NM_001278074.1 | c.5497C>T | p.Pro1833Ser | missense_variant | 66/66 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.5497C>T | p.Pro1833Ser | missense_variant | 66/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.5497C>T | p.Pro1833Ser | missense_variant | 66/66 | 2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727234
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74356
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 27, 2017 | This sequence change replaces proline with serine at codon 1833 of the COL5A1 protein (p.Pro1833Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs370789226, ExAC 0.002%) but 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: "Unknown"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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