rs61733017

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152296.5(ATP1A3):c.2319T>C(p.Asn773Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00276 in 1,614,036 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 29 hom. )

Consequence

ATP1A3
NM_152296.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 4.21

Variant links:

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 links:

ENSG00000285505 (HGNC:):

ENSG00000285505 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 19-41970487-A-G is Benign according to our data. Variant chr19-41970487-A-G is described in ClinVar as [Benign]. Clinvar id is 157925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1743/152142) while in subpopulation AFR AF= 0.0355 (1475/41494). AF 95% confidence interval is 0.034. There are 32 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1743 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1A3	NM_152296.5 link	c.2319T>C	p.Asn773Asn	synonymous_variant	Exon 17 of 23	ENST00000648268.1	NP_689509.1	P13637-1Q53ES0
ATP1A3	NM_001256214.2 link	c.2358T>C	p.Asn786Asn	synonymous_variant	Exon 17 of 23		NP_001243143.1	P13637-3Q53ES0
ATP1A3	NM_001256213.2 link	c.2352T>C	p.Asn784Asn	synonymous_variant	Exon 17 of 23		NP_001243142.1	P13637-2Q53ES0
ATP1A3	XM_047438862.1 link	c.2229T>C	p.Asn743Asn	synonymous_variant	Exon 17 of 23		XP_047294818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1A3	ENST00000648268.1 link	c.2319T>C	p.Asn773Asn	synonymous_variant	Exon 17 of 23		NM_152296.5	ENSP00000498113.1		P13637-1
ENSG00000285505	ENST00000644613.1 link	n.2319T>C		non_coding_transcript_exon_variant	Exon 17 of 25			ENSP00000494711.1		A0A2R8YEY8

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1735

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.0395

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00456

AC:

1148

AN:

251488

Hom.:

AF XY:

0.00369

AC XY:

502

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0359

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.0381

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000492

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00185

AC:

2705

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1233

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0313

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.0357

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000235

Gnomad4 OTH exome

AF:

0.00508

GnomAD4 genome

AF:

0.0115

AC:

1743

AN:

152142

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

849

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0355

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.0395

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00865

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dystonia 12

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 23, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Alternating hemiplegia of childhood 2

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy 99

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ATP1A3-related disorder

Benign:1

Sep 23, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.4

DANN

Benign

0.71

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over