chr11-116821127-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000482.4(APOA4):c.931G>A(p.Gly311Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_000482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOA4 | NM_000482.4 | c.931G>A | p.Gly311Arg | missense_variant | 3/3 | ENST00000357780.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOA4 | ENST00000357780.5 | c.931G>A | p.Gly311Arg | missense_variant | 3/3 | 1 | NM_000482.4 | P1 | |
ENST00000645414.1 | n.276C>T | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250958Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135802
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461520Hom.: 0 Cov.: 86 AF XY: 0.00000963 AC XY: 7AN XY: 727072
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152302Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 09, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with APOA4-related conditions. This variant is present in population databases (rs377752186, gnomAD 0.03%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 311 of the APOA4 protein (p.Gly311Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at