chr9-134805192-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP2PP3_Strong
The NM_000093.5(COL5A1):c.3236C>T(p.Pro1079Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,688 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. P1079S) 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.3236C>T | p.Pro1079Leu | missense_variant | 41/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.3236C>T | p.Pro1079Leu | missense_variant | 41/66 | ||
COL5A1 | XM_017014266.3 | c.3236C>T | p.Pro1079Leu | missense_variant | 41/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.3236C>T | p.Pro1079Leu | missense_variant | 41/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.3236C>T | p.Pro1079Leu | missense_variant | 41/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461688Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727164
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 23, 2023 | Has not been previously published as pathogenic or benign to our knowledge; 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; Occurs in the triple helical domain at the X position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the X position is not a common mechanism of disease (Symoens et al., 2012; HGMD); This variant is associated with the following publications: (PMID: 22696272) - |
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces proline with leucine at codon 1079 of the COL5A1 protein (p.Pro1079Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with COL5A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 212957). 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