10-88732266-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001080518.2(LIPK):c.511C>A(p.His171Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,614 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 (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
LIPK
NM_001080518.2 missense
NM_001080518.2 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 1.31
Genes affected
LIPK (HGNC:23444): (lipase family member K) Predicted to enable lipoprotein lipase activity. Predicted to be involved in cornification. Predicted to be located in extracellular region. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.95
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIPK | NM_001080518.2 | c.511C>A | p.His171Asn | missense_variant | 5/10 | ENST00000404190.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIPK | ENST00000404190.3 | c.511C>A | p.His171Asn | missense_variant | 5/10 | 1 | NM_001080518.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249380Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135258
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461464Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727048
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 09, 2023 | The c.511C>A (p.H171N) alteration is located in exon 4 (coding exon 4) of the LIPK gene. This alteration results from a C to A substitution at nucleotide position 511, causing the histidine (H) at amino acid position 171 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of sheet (P = 0.1907);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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