rs397516783
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_002667.5(PLN):c.152T>C(p.Leu51Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L51F) has been classified as Uncertain significance.
Frequency
Consequence
NM_002667.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLN | NM_002667.5 | c.152T>C | p.Leu51Pro | missense_variant | 2/2 | ENST00000357525.6 | |
CEP85L | NM_001042475.3 | c.1020+6456A>G | intron_variant | ENST00000368491.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLN | ENST00000357525.6 | c.152T>C | p.Leu51Pro | missense_variant | 2/2 | 1 | NM_002667.5 | P1 | |
CEP85L | ENST00000368491.8 | c.1020+6456A>G | intron_variant | 1 | NM_001042475.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457970Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 725632
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 24, 2012 | Variant classified as Uncertain Significance - Favor Pathogenic. The Leu51Pro va riant in PLN has not been reported in the literature and has not been identified in large and broad European and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). This low frequency is co nsistent with a disease causing role but insufficient to establish this with con fidence. Computational analyses (biochemical amino acid properties, conservation , AlignGVGD, PolyPhen2, and SIFT) suggest that the Leu51Pro variant may impact t he protein, though this information is not predictive enough to determine pathog enicity. Additional studies are needed to fully assess the clinical significance of the Leu51Pro variant. - |
Dilated cardiomyopathy 1P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 18, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 51 of the PLN protein (p.Leu51Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 44577). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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