1-11958592-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000302.4(PLOD1):c.920G>A(p.Arg307Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,940 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. R307W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000302.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | c.920G>A | p.Arg307Gln | missense_variant | 9/19 | ENST00000196061.5 | |
PLOD1 | NM_001316320.2 | c.1061G>A | p.Arg354Gln | missense_variant | 10/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061.5 | c.920G>A | p.Arg307Gln | missense_variant | 9/19 | 1 | NM_000302.4 | P1 | |
PLOD1 | ENST00000465920.1 | n.870G>A | non_coding_transcript_exon_variant | 4/4 | 5 | ||||
PLOD1 | ENST00000485046.5 | n.963G>A | non_coding_transcript_exon_variant | 9/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461846Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727224
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74278
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, kyphoscoliotic type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 19, 2021 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 307 of the PLOD1 protein (p.Arg307Gln). This variant is not present in population databases (gnomAD no frequency). 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: 459835). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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