chr1-11958577-C-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000302.4(PLOD1):c.905C>A(p.Ser302Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,614,088 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000302.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLOD1 | NM_000302.4 | c.905C>A | p.Ser302Tyr | missense_variant | 9/19 | ENST00000196061.5 | NP_000293.2 | |
PLOD1 | NM_001316320.2 | c.1046C>A | p.Ser349Tyr | missense_variant | 10/20 | NP_001303249.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLOD1 | ENST00000196061.5 | c.905C>A | p.Ser302Tyr | missense_variant | 9/19 | 1 | NM_000302.4 | ENSP00000196061.4 | ||
PLOD1 | ENST00000465920.1 | n.855C>A | non_coding_transcript_exon_variant | 4/4 | 5 | |||||
PLOD1 | ENST00000485046.5 | n.948C>A | non_coding_transcript_exon_variant | 9/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152146Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000450 AC: 113AN: 251184Hom.: 0 AF XY: 0.000589 AC XY: 80AN XY: 135832
GnomAD4 exome AF: 0.000186 AC: 272AN: 1461824Hom.: 3 Cov.: 33 AF XY: 0.000276 AC XY: 201AN XY: 727218
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152264Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9AN XY: 74454
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, kyphoscoliotic type 1 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | The observed missense c.905C>A(p.Ser302Tyr) variant in PLOD1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is present with an allele frequency of 0.04% in gnomAD Exomes database. This variant has been reported to the ClinVar database as Likely benign,but no details are available for independent assessment. The amino acid change p.Ser302Tyr in PLOD1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ser at position 302 is changed to a Tyr changing protein sequence and it might alter its composition and physico-chemical properties. Computational evidence (Polyphen - Benign, SIFT - Damaging and MutationTaster - Polymorphism) predicts conflicting evidence on protein structure and function for this variant. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS). - |
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at