1-11964188-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000302.4(PLOD1):c.1216C>T(p.Pro406Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,946 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P406A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000302.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | c.1216C>T | p.Pro406Ser | missense_variant | 12/19 | ENST00000196061.5 | |
PLOD1 | NM_001316320.2 | c.1357C>T | p.Pro453Ser | missense_variant | 13/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061.5 | c.1216C>T | p.Pro406Ser | missense_variant | 12/19 | 1 | NM_000302.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251336Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135838
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461688Hom.: 0 Cov.: 36 AF XY: 0.00000550 AC XY: 4AN XY: 727134
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152258Hom.: 0 Cov.: 29 AF XY: 0.0000134 AC XY: 1AN XY: 74448
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 09, 2024 | The p.P406S variant (also known as c.1216C>T), located in coding exon 12 of the PLOD1 gene, results from a C to T substitution at nucleotide position 1216. The proline at codon 406 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Ehlers-Danlos syndrome, kyphoscoliotic type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 406 of the PLOD1 protein (p.Pro406Ser). This variant is present in population databases (rs760764359, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 580095). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at