chr11-116821004-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000482.4(APOA4):c.1054A>T(p.Asn352Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000379 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOA4 | NM_000482.4 | c.1054A>T | p.Asn352Tyr | missense_variant | 3/3 | ENST00000357780.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOA4 | ENST00000357780.5 | c.1054A>T | p.Asn352Tyr | missense_variant | 3/3 | 1 | NM_000482.4 | P1 | |
ENST00000645414.1 | n.169-16T>A | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152226Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000425 AC: 107AN: 251476Hom.: 0 AF XY: 0.000397 AC XY: 54AN XY: 135916
GnomAD4 exome AF: 0.000381 AC: 557AN: 1461888Hom.: 0 Cov.: 86 AF XY: 0.000378 AC XY: 275AN XY: 727244
GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152226Hom.: 0 Cov.: 34 AF XY: 0.000417 AC XY: 31AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2023 | This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 352 of the APOA4 protein (p.Asn352Tyr). This variant is present in population databases (rs147577451, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with APOA4-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on APOA4 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at