rs368998149
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_152296.5(ATP1A3):c.858C>T(p.Thr286=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
ATP1A3
NM_152296.5 synonymous
NM_152296.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.16
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 19-41985053-G-A is Benign according to our data. Variant chr19-41985053-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 536474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.16 with no splicing effect.
BS2
?
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A3 | NM_152296.5 | c.858C>T | p.Thr286= | synonymous_variant | 8/23 | ENST00000648268.1 | |
ATP1A3 | NM_001256214.2 | c.897C>T | p.Thr299= | synonymous_variant | 8/23 | ||
ATP1A3 | NM_001256213.2 | c.891C>T | p.Thr297= | synonymous_variant | 8/23 | ||
ATP1A3 | XM_047438862.1 | c.768C>T | p.Thr256= | synonymous_variant | 8/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A3 | ENST00000648268.1 | c.858C>T | p.Thr286= | synonymous_variant | 8/23 | NM_152296.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152246Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000560 AC: 14AN: 250112Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135234
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461504Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 727014
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dystonia 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 18, 2018 | - - |
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