rs61733017
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_152296.5(ATP1A3):āc.2319T>Cā(p.Asn773=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00276 in 1,614,036 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.011 ( 32 hom., cov: 32)
Exomes š: 0.0019 ( 29 hom. )
Consequence
ATP1A3
NM_152296.5 synonymous
NM_152296.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.21
Genes affected
ATP1A3 (HGNC:801): (ATPase Na+/K+ transporting subunit alpha 3) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 3 subunit. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 19-41970487-A-G is Benign according to our data. Variant chr19-41970487-A-G is described in ClinVar as [Benign]. Clinvar id is 157925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1743/152142) while in subpopulation AFR AF= 0.0355 (1475/41494). AF 95% confidence interval is 0.034. There are 32 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1743 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A3 | NM_152296.5 | c.2319T>C | p.Asn773= | synonymous_variant | 17/23 | ENST00000648268.1 | |
ATP1A3 | NM_001256214.2 | c.2358T>C | p.Asn786= | synonymous_variant | 17/23 | ||
ATP1A3 | NM_001256213.2 | c.2352T>C | p.Asn784= | synonymous_variant | 17/23 | ||
ATP1A3 | XM_047438862.1 | c.2229T>C | p.Asn743= | synonymous_variant | 17/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A3 | ENST00000648268.1 | c.2319T>C | p.Asn773= | synonymous_variant | 17/23 | NM_152296.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0114 AC: 1735AN: 152024Hom.: 30 Cov.: 32
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GnomAD3 exomes AF: 0.00456 AC: 1148AN: 251488Hom.: 14 AF XY: 0.00369 AC XY: 502AN XY: 135922
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GnomAD4 exome AF: 0.00185 AC: 2705AN: 1461894Hom.: 29 Cov.: 34 AF XY: 0.00170 AC XY: 1233AN XY: 727248
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GnomAD4 genome ? AF: 0.0115 AC: 1743AN: 152142Hom.: 32 Cov.: 32 AF XY: 0.0114 AC XY: 849AN XY: 74378
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dystonia 12 Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 23, 2017 | - - |
Alternating hemiplegia of childhood 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2019 | - - |
Developmental and epileptic encephalopathy 99 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
ATP1A3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 23, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at