15-50908845-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007347.5(AP4E1):c.67G>A(p.Gly23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,608,588 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G23R) has been classified as Uncertain significance.
Frequency
Consequence
NM_007347.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP4E1 | NM_007347.5 | c.67G>A | p.Gly23Ser | missense_variant | 1/21 | ENST00000261842.10 | |
AP4E1 | NM_001252127.2 | c.-182G>A | 5_prime_UTR_variant | 1/21 | |||
AP4E1 | XM_005254264.5 | c.-76+202G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP4E1 | ENST00000261842.10 | c.67G>A | p.Gly23Ser | missense_variant | 1/21 | 1 | NM_007347.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152232Hom.: 1 Cov.: 34
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1456356Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 724134
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152232Hom.: 1 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74370
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 13, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 23 of the AP4E1 protein (p.Gly23Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AP4E1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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