rs370300896
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014855.3(AP5Z1):c.1685C>T(p.Ala562Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,611,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. A562A) has been classified as Likely benign.
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.1685C>T | p.Ala562Val | missense_variant | 13/17 | ENST00000649063.2 | |
AP5Z1 | NM_001364858.1 | c.1217C>T | p.Ala406Val | missense_variant | 12/16 | ||
AP5Z1 | XM_047421098.1 | c.1349C>T | p.Ala450Val | missense_variant | 11/15 | ||
AP5Z1 | NR_157345.1 | n.1816C>T | non_coding_transcript_exon_variant | 13/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP5Z1 | ENST00000649063.2 | c.1685C>T | p.Ala562Val | missense_variant | 13/17 | NM_014855.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000372 AC: 9AN: 241920Hom.: 0 AF XY: 0.0000452 AC XY: 6AN XY: 132706
GnomAD4 exome AF: 0.00000891 AC: 13AN: 1459068Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 725900
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74320
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 48 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 567859). This variant has not been reported in the literature in individuals affected with AP5Z1-related conditions. This variant is present in population databases (rs370300896, gnomAD 0.04%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 562 of the AP5Z1 protein (p.Ala562Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at