rs118204065
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000237.3(LPL):c.264T>A(p.Tyr88Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,844 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y88Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000237.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LPL | NM_000237.3 | c.264T>A | p.Tyr88Ter | stop_gained | 3/10 | ENST00000650287.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LPL | ENST00000650287.1 | c.264T>A | p.Tyr88Ter | stop_gained | 3/10 | NM_000237.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251462Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727226
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hyperlipoproteinemia, type I Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 14, 1992 | - - |
Cardiovascular phenotype Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2022 | The p.Y88* pathogenic mutation (also known as c.264T>A), located in coding exon 3 of the LPL gene, results from a T to A substitution at nucleotide position 264. This changes the amino acid from a tyrosine to a stop codon within coding exon 3. This variant (also reported with legacy nomenclature p.Y61*) has been detected in the homozygous state or in trans with another pathogenic LPL variant in multiple individuals with LPL-related chylomicronemia syndrome (Gotoda T et al. J Clin Invest, 1991 12;88:1856-64; Gotoda T et al. Biochim Biophys Acta, 1992 Apr;1138:353-6; Ebara T et al. Atherosclerosis, 2001 Dec;159:375-9; Rabacchi C et al. Atherosclerosis, 2015 Jul;241:79-86; Tanaka S et al. Intern Med, 2019 Jan;58:251-257). In addition to the clinical data in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at