10-89226950-AT-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000235.4(LIPA):βc.482delβ(p.Asn161IlefsTer19) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000149 in 1,613,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. N161N) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000235.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIPA | NM_000235.4 | c.482del | p.Asn161IlefsTer19 | frameshift_variant | 5/10 | ENST00000336233.10 | |
LIPA | NM_001127605.3 | c.482del | p.Asn161IlefsTer19 | frameshift_variant | 5/10 | ||
LIPA | NM_001288979.2 | c.134del | p.Asn45IlefsTer19 | frameshift_variant | 3/8 | ||
LIPA | XM_024448023.2 | c.482del | p.Asn161IlefsTer19 | frameshift_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIPA | ENST00000336233.10 | c.482del | p.Asn161IlefsTer19 | frameshift_variant | 5/10 | 1 | NM_000235.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251412Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135872
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461278Hom.: 0 Cov.: 29 AF XY: 0.0000165 AC XY: 12AN XY: 726978
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Wolman disease Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2023 | This premature translational stop signal has been observed in individual(s) with Wolman disease (PMID: 21963785). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs762559980, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Asn161Ilefs*19) in the LIPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LIPA are known to be pathogenic (PMID: 23485521). ClinVar contains an entry for this variant (Variation ID: 552285). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2011 | - - |
Lysosomal acid lipase deficiency Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 17, 2020 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jun 02, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at