9-134802963-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BS2
The NM_000093.5(COL5A1):c.3082C>T(p.Leu1028Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,456,628 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. L1028L) 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_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.3082C>T | p.Leu1028Phe | missense_variant | 39/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.3082C>T | p.Leu1028Phe | missense_variant | 39/66 | ||
COL5A1 | XM_017014266.3 | c.3082C>T | p.Leu1028Phe | missense_variant | 39/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.3082C>T | p.Leu1028Phe | missense_variant | 39/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.3082C>T | p.Leu1028Phe | missense_variant | 39/66 | 2 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000847 AC: 2AN: 236132Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 128108
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456628Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3AN XY: 723984
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 | Apr 06, 2017 | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with an uncertain effect 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. The frequency data for this variant (rs762810181) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a COL5A1-related disease. This sequence change replaces leucine with phenylalanine at codon 1028 of the COL5A1 protein (p.Leu1028Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at