rs747393648
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000302.4(PLOD1):āc.2057A>Gā(p.Asn686Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,522 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N686K) 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 Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | c.2057A>G | p.Asn686Ser | missense_variant | 19/19 | ENST00000196061.5 | |
PLOD1 | NM_001316320.2 | c.2198A>G | p.Asn733Ser | missense_variant | 20/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061.5 | c.2057A>G | p.Asn686Ser | missense_variant | 19/19 | 1 | NM_000302.4 | P1 | |
PLOD1 | ENST00000481933.1 | n.1484A>G | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
PLOD1 | ENST00000491536.5 | n.384-602A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151836Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250778Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135696
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461686Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727142
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 151836Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74158
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 01, 2023 | The p.N686S variant (also known as c.2057A>G), located in coding exon 19 of the PLOD1 gene, results from an A to G substitution at nucleotide position 2057. The asparagine at codon 686 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. 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. - |
Ehlers-Danlos syndrome, kyphoscoliotic type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces asparagine with serine at codon 686 of the PLOD1 protein (p.Asn686Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs747393648, ExAC 0.07%). 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: 459818). 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: "Deleterious"; 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