rs376070950
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_022089.4(ATP13A2):c.1895C>T(p.Ser632Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S632S) has been classified as Uncertain significance.
Frequency
Consequence
NM_022089.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP13A2 | NM_022089.4 | c.1895C>T | p.Ser632Leu | missense_variant | 18/29 | ENST00000326735.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP13A2 | ENST00000326735.13 | c.1895C>T | p.Ser632Leu | missense_variant | 18/29 | 1 | NM_022089.4 | A1 | |
ENST00000446261.1 | n.188-12290G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152268Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000243 AC: 6AN: 247128Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134096
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1460900Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 726758
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74396
ClinVar
Submissions by phenotype
Kufor-Rakeb syndrome;C5567893:Autosomal recessive spastic paraplegia type 78 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces serine with leucine at codon 632 of the ATP13A2 protein (p.Ser632Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs376070950, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with ATP13A2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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