rs1554805618
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_000093.5(COL5A1):c.3911C>T(p.Pro1304Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P1304P) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.3911C>T | p.Pro1304Leu | missense_variant | 50/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.3911C>T | p.Pro1304Leu | missense_variant | 50/66 | ||
COL5A1 | XM_017014266.3 | c.3911C>T | p.Pro1304Leu | missense_variant | 50/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.3911C>T | p.Pro1304Leu | missense_variant | 50/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.3911C>T | p.Pro1304Leu | missense_variant | 50/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 7.15e-7 AC: 1AN: 1399272Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 690212
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 | Jun 19, 2021 | This variant has not been reported in the literature in individuals with COL5A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 459684). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL5A1 protein function. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 1304 of the COL5A1 protein (p.Pro1304Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at