rs774068163
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014855.3(AP5Z1):c.740G>A(p.Arg247Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000375 in 1,600,998 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R247W) has been classified as Uncertain significance.
Frequency
Consequence
NM_014855.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP5Z1 | NM_014855.3 | c.740G>A | p.Arg247Gln | missense_variant | 6/17 | ENST00000649063.2 | |
AP5Z1 | NM_001364858.1 | c.272G>A | p.Arg91Gln | missense_variant | 5/16 | ||
AP5Z1 | XM_047421098.1 | c.404G>A | p.Arg135Gln | missense_variant | 4/15 | ||
AP5Z1 | NR_157345.1 | n.833G>A | non_coding_transcript_exon_variant | 6/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP5Z1 | ENST00000649063.2 | c.740G>A | p.Arg247Gln | missense_variant | 6/17 | NM_014855.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000315 AC: 7AN: 222384Hom.: 0 AF XY: 0.0000164 AC XY: 2AN XY: 121882
GnomAD4 exome AF: 0.0000283 AC: 41AN: 1448890Hom.: 0 Cov.: 39 AF XY: 0.0000208 AC XY: 15AN XY: 719754
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152108Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74284
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 48 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 247 of the AP5Z1 protein (p.Arg247Gln). This variant is present in population databases (rs774068163, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with AP5Z1-related conditions. ClinVar contains an entry for this variant (Variation ID: 487226). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 25, 2022 | The c.740G>A (p.R247Q) alteration is located in exon 6 (coding exon 6) of the AP5Z1 gene. This alteration results from a G to A substitution at nucleotide position 740, causing the arginine (R) at amino acid position 247 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at