1-116399068-AC-CG

Variant names:

• chr1-116399068-AC-CG
• NM_000701.8:c.2432_2433delACinsCG
• ATP1A1 p.Asp811Ala

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PS1_Moderate PP3

The NM_000701.8(ATP1A1):​c.2432_2433delACinsCG​(p.Asp811Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP1A1 NM_000701.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

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]

ATP1A1-AS1 (HGNC:28262): (ATP1A1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PS1: Transcript NM_000701.8 (ATP1A1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000701.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1	NM_000701.8	MANE Select	c.2432_2433delACinsCG	p.Asp811Ala	missense	N/A	NP_000692.2
	ATP1A1	NM_001160233.2		c.2432_2433delACinsCG	p.Asp811Ala	missense	N/A	NP_001153705.1	P05023-4
	ATP1A1	NM_001160234.2		c.2339_2340delACinsCG	p.Asp780Ala	missense	N/A	NP_001153706.1	P05023-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1	ENST00000295598.10	TSL:1 MANE Select	c.2432_2433delACinsCG	p.Asp811Ala	missense	N/A	ENSP00000295598.5	P05023-1
	ATP1A1-AS1	ENST00000493908.2	TSL:1	n.659_660delGTinsCG		non_coding_transcript_exon	Exon 3 of 3
	ATP1A1-AS1	ENST00000608511.6	TSL:1	n.410+1827_410+1828delGTinsCG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-116941690;