rs786205872
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_001084.5(PLOD3):c.2071delT(p.Cys691AlafsTer9) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
PLOD3
NM_001084.5 frameshift
NM_001084.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.22
Publications
2 publications found
Genes affected
PLOD3 (HGNC:9083): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 3) The protein encoded by this gene is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VIB have deficiencies in lysyl hydroxylase activity. [provided by RefSeq, Jul 2008]
PLOD3 Gene-Disease associations (from GenCC):
- bone fragility with contractures, arterial rupture, and deafnessInheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0659 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-101206426-CA-C is Pathogenic according to our data. Variant chr7-101206426-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 6644.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001084.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PLOD3 | NM_001084.5 | MANE Select | c.2071delT | p.Cys691AlafsTer9 | frameshift | Exon 19 of 19 | NP_001075.1 | O60568 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PLOD3 | ENST00000223127.8 | TSL:1 MANE Select | c.2071delT | p.Cys691AlafsTer9 | frameshift | Exon 19 of 19 | ENSP00000223127.3 | O60568 | |
| PLOD3 | ENST00000890272.1 | c.2143delT | p.Cys715AlafsTer9 | frameshift | Exon 20 of 20 | ENSP00000560331.1 | |||
| PLOD3 | ENST00000890269.1 | c.2071delT | p.Cys691AlafsTer9 | frameshift | Exon 20 of 20 | ENSP00000560328.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453720Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 722738 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1453720
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
722738
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33298
American (AMR)
AF:
AC:
0
AN:
42372
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25944
East Asian (EAS)
AF:
AC:
0
AN:
39378
South Asian (SAS)
AF:
AC:
0
AN:
85738
European-Finnish (FIN)
AF:
AC:
0
AN:
52552
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1108552
Other (OTH)
AF:
AC:
0
AN:
60126
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Bone fragility with contractures, arterial rupture, and deafness (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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