7-4781717-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014855.3(AP5Z1):c.329G>A(p.Arg110Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000543 in 1,582,346 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. R110W) has been classified as Uncertain significance.
Frequency
Consequence
NM_014855.3 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 |
---|---|---|---|---|---|---|---|
AP5Z1 | NM_014855.3 | c.329G>A | p.Arg110Gln | missense_variant | 3/17 | ENST00000649063.2 | |
AP5Z1 | NM_001364858.1 | c.-103+405G>A | intron_variant | ||||
AP5Z1 | NR_157345.1 | n.422G>A | non_coding_transcript_exon_variant | 3/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP5Z1 | ENST00000649063.2 | c.329G>A | p.Arg110Gln | missense_variant | 3/17 | NM_014855.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000709 AC: 17AN: 239802Hom.: 0 AF XY: 0.0000611 AC XY: 8AN XY: 130850
GnomAD4 exome AF: 0.0000510 AC: 73AN: 1430010Hom.: 1 Cov.: 31 AF XY: 0.0000525 AC XY: 37AN XY: 704310
GnomAD4 genome AF: 0.0000853 AC: 13AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74490
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 48 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 110 of the AP5Z1 protein (p.Arg110Gln). This variant is present in population databases (rs201481802, gnomAD 0.03%). 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: 240942). 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 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. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Sep 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at