chr13-43881274-GA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_153218.4(LACC1):c.296del(p.Asn99IlefsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
LACC1
NM_153218.4 frameshift
NM_153218.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.22
Genes affected
LACC1 (HGNC:26789): (laccase domain containing 1) This gene encodes an oxidoreductase that promotes fatty-acid oxidation, with concomitant inflammasome activation, mitochondrial and NADPH-oxidase-dependent reactive oxygen species production, and bactericidal activity of macrophages. The encoded protein forms a complex with fatty acid synthase on peroxisomes and is thought to be modulated by peroxisome proliferator-activated receptor signaling events. Naturally occurring mutations in this gene are associated with inflammatory bowel disease, Behcet's disease, leprosy, ulcerative colitis, early-onset Crohn's disease, and systemic juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 13-43881274-GA-G is Pathogenic according to our data. Variant chr13-43881274-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 2202782.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LACC1 | NM_153218.4 | c.296del | p.Asn99IlefsTer2 | frameshift_variant | 2/7 | ENST00000325686.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LACC1 | ENST00000325686.7 | c.296del | p.Asn99IlefsTer2 | frameshift_variant | 2/7 | 1 | NM_153218.4 | P1 | |
LACC1 | ENST00000441843.5 | c.296del | p.Asn99IlefsTer2 | frameshift_variant | 2/7 | 5 | P1 | ||
LACC1 | ENST00000425906.1 | c.296del | p.Asn99IlefsTer2 | frameshift_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2022 | This sequence change creates a premature translational stop signal (p.Asn99Ilefs*2) in the LACC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LACC1 are known to be pathogenic (PMID: 27881174, 30872671). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LACC1-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Calibrated prediction
Score
Prediction
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
Publications
No publications associated with this variant yet.