chr19-41975770-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_Strong
The NM_152296.5(ATP1A3):c.2122G>A(p.Gly708Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G708G) has been classified as Likely benign.
Frequency
Consequence
NM_152296.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A3 | NM_152296.5 | c.2122G>A | p.Gly708Ser | missense_variant | 16/23 | ENST00000648268.1 | |
ATP1A3 | NM_001256214.2 | c.2161G>A | p.Gly721Ser | missense_variant | 16/23 | ||
ATP1A3 | NM_001256213.2 | c.2155G>A | p.Gly719Ser | missense_variant | 16/23 | ||
ATP1A3 | XM_047438862.1 | c.2032G>A | p.Gly678Ser | missense_variant | 16/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A3 | ENST00000648268.1 | c.2122G>A | p.Gly708Ser | missense_variant | 16/23 | NM_152296.5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Dystonia 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 26, 2016 | This sequence change replaces glycine with serine at codon 708 of the ATP1A3 protein (p.Gly708Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATP1A3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. 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