rs118204072

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000237.3(LPL):​c.596C>A​(p.Ser199Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

LPL
NM_000237.3 missense

Scores

15
3
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.52
Variant links:
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LPLNM_000237.3 linkuse as main transcriptc.596C>A p.Ser199Tyr missense_variant 5/10 ENST00000650287.1 NP_000228.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LPLENST00000650287.1 linkuse as main transcriptc.596C>A p.Ser199Tyr missense_variant 5/10 NM_000237.3 ENSP00000497642 P1
LPLENST00000520959.5 linkuse as main transcript downstream_gene_variant 4 ENSP00000428496

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.45
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.86
D;D
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
.;D
M_CAP
Pathogenic
0.43
D
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Pathogenic
0.95
D
MutationAssessor
Pathogenic
3.1
M;M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-5.8
D;.
REVEL
Pathogenic
0.78
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.0020
D;.
Polyphen
1.0
D;D
Vest4
0.90
MutPred
0.67
Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);
MVP
0.98
MPC
0.50
ClinPred
1.0
D
GERP RS
6.2
Varity_R
0.95
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-19811685; API