rs1277995091
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_000093.5(COL5A1):c.256C>T(p.Pro86Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,318 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. P86R) has been classified as Benign.
Frequency
Consequence
NM_000093.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.256C>T | p.Pro86Ser | missense_variant | 2/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.256C>T | p.Pro86Ser | missense_variant | 2/66 | ||
COL5A1 | XM_017014266.3 | c.256C>T | p.Pro86Ser | missense_variant | 2/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.256C>T | p.Pro86Ser | missense_variant | 2/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.256C>T | p.Pro86Ser | missense_variant | 2/66 | 2 | A2 | ||
COL5A1 | ENST00000464187.1 | n.442C>T | non_coding_transcript_exon_variant | 2/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461044Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726822
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74398
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces proline with serine at codon 86 of the COL5A1 protein (p.Pro86Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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