rs763409574
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000302.4(PLOD1):āc.1172A>Gā(p.Asn391Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,600,930 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N391K) has been classified as Likely benign.
Frequency
Consequence
NM_000302.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | c.1172A>G | p.Asn391Ser | missense_variant | 11/19 | ENST00000196061.5 | NP_000293.2 | |
PLOD1 | NM_001316320.2 | c.1313A>G | p.Asn438Ser | missense_variant | 12/20 | NP_001303249.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061.5 | c.1172A>G | p.Asn391Ser | missense_variant | 11/19 | 1 | NM_000302.4 | ENSP00000196061.4 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152122Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000216 AC: 49AN: 227248Hom.: 0 AF XY: 0.000221 AC XY: 27AN XY: 122424
GnomAD4 exome AF: 0.000107 AC: 155AN: 1448808Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 72AN XY: 719362
GnomAD4 genome AF: 0.000177 AC: 27AN: 152122Hom.: 2 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74310
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, kyphoscoliotic type 1 Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | PG23_Medical Genetics Lab, ASST Papa Giovanni XXIII | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2024 | The p.N391S variant (also known as c.1172A>G), located in coding exon 11 of the PLOD1 gene, results from an A to G substitution at nucleotide position 1172. The asparagine at codon 391 is replaced by serine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species, and serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 25, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
PLOD1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 17, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at