rs121912503
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_005577.4(LPA):c.109C>T(p.Arg37Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000421 in 1,613,688 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 1 hom. )
Consequence
LPA
NM_005577.4 stop_gained
NM_005577.4 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 3.63
Genes affected
LPA (HGNC:6667): (lipoprotein(a)) The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-160650438-G-A is Pathogenic according to our data. Variant chr6-160650438-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 14450.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-160650438-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LPA | NM_005577.4 | c.109C>T | p.Arg37Ter | stop_gained | 2/39 | ENST00000316300.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LPA | ENST00000316300.10 | c.109C>T | p.Arg37Ter | stop_gained | 2/39 | 1 | NM_005577.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251098Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135882
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GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461570Hom.: 1 Cov.: 32 AF XY: 0.0000495 AC XY: 36AN XY: 727106
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74288
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Lipoprotein(a) deficiency, congenital Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2004 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
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Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MutationTaster
Benign
A;A
Vest4
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at