rs377062537
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 3P and 7B. PM1PP2BP4_ModerateBP6BS2
The NM_000093.5(COL5A1):c.4433C>T(p.Pro1478Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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 Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.4433C>T | p.Pro1478Leu | missense_variant | 57/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.4433C>T | p.Pro1478Leu | missense_variant | 57/66 | ||
COL5A1 | XM_017014266.3 | c.4433C>T | p.Pro1478Leu | missense_variant | 57/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.4433C>T | p.Pro1478Leu | missense_variant | 57/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.4433C>T | p.Pro1478Leu | missense_variant | 57/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250012Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135342
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461044Hom.: 0 Cov.: 34 AF XY: 0.00000826 AC XY: 6AN XY: 726822
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74454
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 13, 2023 | The p.P1478L variant (also known as c.4433C>T), located in coding exon 57 of the COL5A1 gene, results from a C to T substitution at nucleotide position 4433. The proline at codon 1478 is replaced by leucine, an amino acid with similar properties. 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. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at