19-41966938-C-CAGT

Position:

• chr19-41966938-C-CAGT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_152296.5(ATP1A3):​c.3040_3041insACT​(p.Tyr1013dup) variant causes a inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATP1A3 NM_152296.5 inframe_insertion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_152296.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 19-41966938-C-CAGT is Pathogenic according to our data. Variant chr19-41966938-C-CAGT is described in ClinVar as [Pathogenic]. Clinvar id is 161154.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1A3	NM_152296.5	c.3040_3041insACT	p.Tyr1013dup	inframe_insertion	23/23	ENST00000648268.1
ATP1A3	NM_001256213.2	c.3073_3074insACT	p.Tyr1024dup	inframe_insertion	23/23
ATP1A3	NM_001256214.2	c.3079_3080insACT	p.Tyr1026dup	inframe_insertion	23/23
ATP1A3	XM_047438862.1	c.2950_2951insACT	p.Tyr983dup	inframe_insertion	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1A3	ENST00000648268.1	c.3040_3041insACT	p.Tyr1013dup	inframe_insertion	23/23		NM_152296.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dystonia 12 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs397515382; hg19: chr19-42471090;