rs1060502249
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP2PP3BP6
The NM_000093.5(COL5A1):c.3037G>A(p.Glu1013Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,122 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000093.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.3037G>A | p.Glu1013Lys | missense_variant | 39/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.3037G>A | p.Glu1013Lys | missense_variant | 39/66 | ||
COL5A1 | XM_017014266.3 | c.3037G>A | p.Glu1013Lys | missense_variant | 39/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.3037G>A | p.Glu1013Lys | missense_variant | 39/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.3037G>A | p.Glu1013Lys | missense_variant | 39/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245442Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133416
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460122Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726192
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2023 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); 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); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
COL5A1-related condition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 11, 2023 | The COL5A1 c.3037G>A variant is predicted to result in the amino acid substitution p.Glu1013Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-137694764-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at