rs919390
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_152296.5(ATP1A3):c.*39C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,550,440 control chromosomes in the GnomAD database, including 338,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.69 ( 36179 hom., cov: 27)
Exomes 𝑓: 0.66 ( 302255 hom. )
Consequence
ATP1A3
NM_152296.5 3_prime_UTR
NM_152296.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.92
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=-0.58).
BP6
?
Variant 19-41966898-G-C is Benign according to our data. Variant chr19-41966898-G-C is described in ClinVar as [Benign]. Clinvar id is 329400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-41966898-G-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A3 | NM_152296.5 | c.*39C>G | 3_prime_UTR_variant | 23/23 | ENST00000648268.1 | ||
ATP1A3 | NM_001256213.2 | c.*39C>G | 3_prime_UTR_variant | 23/23 | |||
ATP1A3 | NM_001256214.2 | c.*39C>G | 3_prime_UTR_variant | 23/23 | |||
ATP1A3 | XM_047438862.1 | c.*39C>G | 3_prime_UTR_variant | 23/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A3 | ENST00000648268.1 | c.*39C>G | 3_prime_UTR_variant | 23/23 | NM_152296.5 |
Frequencies
GnomAD3 genomes ? AF: 0.687 AC: 103955AN: 151274Hom.: 36156 Cov.: 27
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GnomAD3 exomes AF: 0.653 AC: 100268AN: 153474Hom.: 33040 AF XY: 0.646 AC XY: 52348AN XY: 81082
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GnomAD4 exome AF: 0.656 AC: 917568AN: 1399050Hom.: 302255 Cov.: 64 AF XY: 0.652 AC XY: 450212AN XY: 690022
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GnomAD4 genome ? AF: 0.687 AC: 104018AN: 151390Hom.: 36179 Cov.: 27 AF XY: 0.685 AC XY: 50677AN XY: 73962
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Alternating hemiplegia of childhood 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 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. - |
Dystonia 12 Benign:2
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 | Jul 14, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 15, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 84% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 78. Only high quality variants are reported. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
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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