1-116384061-T-TAAAAAGGGC
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_000701.8(ATP1A1):c.75_83dup(p.Gly26_Lys28dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.0000229 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
ATP1A1
NM_000701.8 inframe_insertion
NM_000701.8 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.02
Genes affected
ATP1A1 (HGNC:799): (ATPase Na+/K+ transporting subunit alpha 1) 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 1 subunit. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_000701.8.
BS2
High AC in GnomAdExome4 at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATP1A1 | NM_000701.8 | c.75_83dup | p.Gly26_Lys28dup | inframe_insertion | 2/23 | ENST00000295598.10 | NP_000692.2 | |
ATP1A1 | NM_001160233.2 | c.75_83dup | p.Gly26_Lys28dup | inframe_insertion | 2/23 | NP_001153705.1 | ||
ATP1A1 | NM_001160234.2 | c.-19_-11dup | 5_prime_UTR_variant | 2/23 | NP_001153706.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATP1A1 | ENST00000295598.10 | c.75_83dup | p.Gly26_Lys28dup | inframe_insertion | 2/23 | 1 | NM_000701.8 | ENSP00000295598 | P4 | |
ATP1A1-AS1 | ENST00000675607.1 | n.386-4017_386-4016insGCCCTTTTT | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151986Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251420Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
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GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461822Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 727210
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151986Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74220
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 05, 2024 | This variant, c.75_83dup, results in the insertion of 3 amino acid(s) of the ATP1A1 protein (p.Gly26_Lys28dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ATP1A1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at