rs200678853
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting
The NM_007347.5(AP4E1):c.1424C>T(p.Ala475Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,610,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A475A) has been classified as Likely benign.
Frequency
Consequence
NM_007347.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP4E1 | NM_007347.5 | c.1424C>T | p.Ala475Val | missense_variant | 12/21 | ENST00000261842.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP4E1 | ENST00000261842.10 | c.1424C>T | p.Ala475Val | missense_variant | 12/21 | 1 | NM_007347.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000203 AC: 51AN: 250944Hom.: 0 AF XY: 0.000273 AC XY: 37AN XY: 135596
GnomAD4 exome AF: 0.000116 AC: 169AN: 1458604Hom.: 0 Cov.: 29 AF XY: 0.000165 AC XY: 120AN XY: 725858
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74280
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 07, 2015 | - - |
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 19, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 434240). This variant has not been reported in the literature in individuals affected with AP4E1-related conditions. This variant is present in population databases (rs200678853, gnomAD 0.1%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 475 of the AP4E1 protein (p.Ala475Val). 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