1-156591932-C-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_144772.3(NAXE):c.128C>A(p.Ser43Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,680 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
NAXE
NM_144772.3 stop_gained
NM_144772.3 stop_gained
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 0.522
Genes affected
NAXE (HGNC:18453): (NAD(P)HX epimerase) The product of this gene interacts with apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoproteins (HDLs). It is secreted into some bodily fluids, and its synthesis and secretion are stimulated in vitro by incubating cells with apoA-I. The human genome contains related pseudogenes. [provided by RefSeq, Jul 2008]
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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 1-156591932-C-A is Pathogenic according to our data. Variant chr1-156591932-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 2506103.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAXE | NM_144772.3 | c.128C>A | p.Ser43Ter | stop_gained | 1/6 | ENST00000368235.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAXE | ENST00000368235.8 | c.128C>A | p.Ser43Ter | stop_gained | 1/6 | 1 | NM_144772.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152182Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000287 AC: 7AN: 243714Hom.: 0 AF XY: 0.0000300 AC XY: 4AN XY: 133436
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GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460498Hom.: 0 Cov.: 82 AF XY: 0.00000826 AC XY: 6AN XY: 726598
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 10, 2023 | Variant summary: APOA1BP c.128C>A (p.Ser43X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.3e-05 in 275032 control chromosomes. c.128C>A has been reported in the literature in individuals affected with Progressive myoclonus epilepsies (Courage_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 33798445). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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