rs770793962
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_000093.5(COL5A1):c.1283C>T(p.Ser428Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S428S) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.1283C>T | p.Ser428Leu | missense_variant | 8/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.1283C>T | p.Ser428Leu | missense_variant | 8/66 | ||
COL5A1 | XM_017014266.3 | c.1283C>T | p.Ser428Leu | missense_variant | 8/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.1283C>T | p.Ser428Leu | missense_variant | 8/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.1283C>T | p.Ser428Leu | missense_variant | 8/66 | 2 | A2 | ||
COL5A1 | ENST00000469093.1 | n.22C>T | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152190Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000643 AC: 16AN: 248950Hom.: 0 AF XY: 0.0000816 AC XY: 11AN XY: 134780
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461840Hom.: 0 Cov.: 33 AF XY: 0.0000509 AC XY: 37AN XY: 727228
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152190Hom.: 0 Cov.: 34 AF XY: 0.0000942 AC XY: 7AN XY: 74338
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2023 | The p.S428L variant (also known as c.1283C>T), located in coding exon 8 of the COL5A1 gene, results from a C to T substitution at nucleotide position 1283. The serine at codon 428 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported in a whole exome sequencing cohort (Stranneheim H et al. Genome Med, 2021 Mar;13:40). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2019 | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Jun 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at