rs962170388
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_000093.5(COL5A1):c.1291G>A(p.Gly431Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000308 in 1,461,782 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
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.1291G>A | p.Gly431Arg | missense_variant | Exon 8 of 66 | ENST00000371817.8 | NP_000084.3 | |
COL5A1 | NM_001278074.1 | c.1291G>A | p.Gly431Arg | missense_variant | Exon 8 of 66 | NP_001265003.1 | ||
COL5A1 | XM_017014266.3 | c.1291G>A | p.Gly431Arg | missense_variant | Exon 8 of 65 | XP_016869755.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.1291G>A | p.Gly431Arg | missense_variant | Exon 8 of 66 | 1 | NM_000093.5 | ENSP00000360882.3 | ||
COL5A1 | ENST00000371820.4 | c.1291G>A | p.Gly431Arg | missense_variant | Exon 8 of 66 | 2 | ENSP00000360885.4 | |||
COL5A1 | ENST00000469093.1 | n.30G>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248882Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134748
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461782Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727194
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:2
Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; Stenson et al., 2014); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 459654; Landrum et al., 2016) -
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Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
The p.G431R variant (also known as c.1291G>A), located in coding exon 8 of the COL5A1 gene, results from a G to A substitution at nucleotide position 1291. The glycine at codon 431 is replaced by arginine, an amino acid with dissimilar properties. This variant has been reported in a coronary artery dissection cohort and in a high myopia cohort (Zekavat SM et al. JAMA Cardiol, 2022 Apr;7:396-406; Liu Y et al. Sci Rep, 2023 Oct;13:18347). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -
Ehlers-Danlos syndrome, classic type Uncertain:1
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Ehlers-Danlos syndrome, classic type, 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at