1-11934761-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000302.4(PLOD1):c.-19C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000583 in 1,373,358 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000058 ( 1 hom. )
Consequence
PLOD1
NM_000302.4 5_prime_UTR_premature_start_codon_gain
NM_000302.4 5_prime_UTR_premature_start_codon_gain
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0440
Genes affected
PLOD1 (HGNC:9081): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 1) Lysyl hydroxylase is a membrane-bound homodimeric protein localized to the cisternae of the 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 VI have deficiencies in lysyl hydroxylase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | c.-19C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/19 | ENST00000196061.5 | NP_000293.2 | ||
PLOD1 | NM_000302.4 | c.-19C>T | 5_prime_UTR_variant | 1/19 | ENST00000196061.5 | NP_000293.2 | ||
PLOD1 | NM_001316320.2 | c.-19C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/20 | NP_001303249.1 | |||
PLOD1 | NM_001316320.2 | c.-19C>T | 5_prime_UTR_variant | 1/20 | NP_001303249.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061 | c.-19C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/19 | 1 | NM_000302.4 | ENSP00000196061.4 | |||
PLOD1 | ENST00000196061 | c.-19C>T | 5_prime_UTR_variant | 1/19 | 1 | NM_000302.4 | ENSP00000196061.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000167 AC: 2AN: 120010Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 65766
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GnomAD4 exome AF: 0.00000583 AC: 8AN: 1373358Hom.: 1 Cov.: 31 AF XY: 0.00000295 AC XY: 2AN XY: 677600
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GnomAD4 genome Cov.: 32
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32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 21, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at