rs118204079
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_000237.3(LPL):c.1334G>A(p.Cys445Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. C445C) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
LPL
NM_000237.3 missense
NM_000237.3 missense
Scores
11
6
1
Clinical Significance
Conservation
PhyloP100: 7.18
Genes affected
LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.986
PP5
?
Variant 8-19962126-G-A is Pathogenic according to our data. Variant chr8-19962126-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1553.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LPL | NM_000237.3 | c.1334G>A | p.Cys445Tyr | missense_variant | 9/10 | ENST00000650287.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LPL | ENST00000650287.1 | c.1334G>A | p.Cys445Tyr | missense_variant | 9/10 | NM_000237.3 | P1 | ||
LPL | ENST00000650478.1 | c.*157G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hyperlipoproteinemia, type I Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 03, 1996 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;.
Polyphen
D;D
Vest4
MutPred
Gain of ubiquitination at K449 (P = 0.0471);Gain of ubiquitination at K449 (P = 0.0471);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at