rs752334702
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The ENST00000371817.8(COL5A1):c.4307C>T(p.Pro1436Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000862 in 1,611,614 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). Synonymous variant affecting the same amino acid position (i.e. P1436P) has been classified as Likely benign.
Frequency
Consequence
ENST00000371817.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.4307C>T | p.Pro1436Leu | missense_variant | 55/66 | ENST00000371817.8 | NP_000084.3 | |
COL5A1 | NM_001278074.1 | c.4307C>T | p.Pro1436Leu | missense_variant | 55/66 | NP_001265003.1 | ||
COL5A1 | XM_017014266.3 | c.4307C>T | p.Pro1436Leu | missense_variant | 55/65 | XP_016869755.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.4307C>T | p.Pro1436Leu | missense_variant | 55/66 | 1 | NM_000093.5 | ENSP00000360882 | P4 | |
COL5A1 | ENST00000371820.4 | c.4307C>T | p.Pro1436Leu | missense_variant | 55/66 | 2 | ENSP00000360885 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000724 AC: 11AN: 151990Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000245 AC: 6AN: 244540Hom.: 0 AF XY: 0.0000300 AC XY: 4AN XY: 133272
GnomAD4 exome AF: 0.0000877 AC: 128AN: 1459624Hom.: 0 Cov.: 33 AF XY: 0.0000923 AC XY: 67AN XY: 726048
GnomAD4 genome AF: 0.0000724 AC: 11AN: 151990Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74250
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 03, 2023 | The p.P1436L variant (also known as c.4307C>T), located in coding exon 55 of the COL5A1 gene, results from a C to T substitution at nucleotide position 4307. The proline at codon 1436 is replaced by leucine, an amino acid with similar properties. This alteration has been reported in a subject with internal carotid artery dissection (Härtl J et al. J Neurol, 2023 Mar;270:1501-1511). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 29, 2024 | Identified in a patient with ischemic stroke and internal carotid artery dissection (PMID: 36411388); 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 (PMID: 22696272; HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22696272, 36411388) - |
Ehlers-Danlos syndrome, classic type, 1;C5543412:Fibromuscular dysplasia, multifocal Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 15, 2021 | - - |
Connective tissue disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 17, 2023 | - - |
Ehlers-Danlos syndrome, classic type Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 10-21-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at