19-41966810-T-A

Variant names:

• chr19-41966810-T-A
• rs782239785
• NM_152296.5:c.*127A>T

Variant summary

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

The NM_152296.5(ATP1A3):​c.*127A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP1A3 NM_152296.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 3 publications found

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]

ATP1A3 Gene-Disease associations (from GenCC):

• alternating hemiplegia of childhood 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• ATP1A3-associated neurological disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• developmental and epileptic encephalopathy 99

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• dystonia 12

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• encephalopathy, acute, infection-induced

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• alternating hemiplegia of childhood

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000285505 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152296.5. 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
	ATP1A3	NM_152296.5	MANE Select	c.*127A>T		3_prime_UTR	Exon 23 of 23	NP_689509.1	P13637-1
	ATP1A3	NM_001256214.2		c.*127A>T		3_prime_UTR	Exon 23 of 23	NP_001243143.1	P13637-3
	ATP1A3	NM_001256213.2		c.*127A>T		3_prime_UTR	Exon 23 of 23	NP_001243142.1	P13637-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A3	ENST00000648268.1	MANE Select	c.*127A>T		3_prime_UTR	Exon 23 of 23	ENSP00000498113.1	P13637-1
	ENSG00000285505	ENST00000644613.1		n.3013+439A>T		intron	N/A	ENSP00000494711.1	A0A2R8YEY8
	ATP1A3	ENST00000545399.6	TSL:2	c.*127A>T		3_prime_UTR	Exon 23 of 23	ENSP00000444688.1	P13637-3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 37186 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 737276 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 363258

African (AFR) AF: 0.00 AC: 0 AN: 20286

American (AMR) AF: 0.00 AC: 0 AN: 24672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16600

East Asian (EAS) AF: 0.00 AC: 0 AN: 26782

South Asian (SAS) AF: 0.00 AC: 0 AN: 33252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2438

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 548966

Other (OTH) AF: 0.00 AC: 0 AN: 32990

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 37186 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 17688

African (AFR) AF: 0.00 AC: 0 AN: 9532

American (AMR) AF: 0.00 AC: 0 AN: 3312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 928

East Asian (EAS) AF: 0.00 AC: 0 AN: 1290

South Asian (SAS) AF: 0.00 AC: 0 AN: 1044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 56

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 17942

Other (OTH) AF: 0.00 AC: 0 AN: 434

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.54
PhyloP100		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs782239785; hg19: chr19-42470962;