19-41966898-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152296.5(ATP1A3):c.*39C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,550,440 control chromosomes in the GnomAD database, including 338,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36179 hom., cov: 27)

Exomes 𝑓: 0.66 ( 302255 hom. )

Consequence

ATP1A3
NM_152296.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.92

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=-0.58).

BP6

Variant 19-41966898-G-C is Benign according to our data. Variant chr19-41966898-G-C is described in ClinVar as [Benign]. Clinvar id is 329400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-41966898-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ATP1A3	NM_152296.5 link	c.*39C>G	3_prime_UTR_variant	Exon 23 of 23	ENST00000648268.1	NP_689509.1	P13637-1Q53ES0
ATP1A3	NM_001256214.2 link	c.*39C>G	3_prime_UTR_variant	Exon 23 of 23		NP_001243143.1	P13637-3Q53ES0
ATP1A3	NM_001256213.2 link	c.*39C>G	3_prime_UTR_variant	Exon 23 of 23		NP_001243142.1	P13637-2Q53ES0
ATP1A3	XM_047438862.1 link	c.*39C>G	3_prime_UTR_variant	Exon 23 of 23		XP_047294818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1A3	ENST00000648268 link	c.*39C>G		3_prime_UTR_variant	Exon 23 of 23		NM_152296.5	ENSP00000498113.1		P13637-1
ENSG00000285505	ENST00000644613.1 link	n.3013+351C>G		intron_variant	Intron 22 of 24			ENSP00000494711.1		A0A2R8YEY8

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

103955

AN:

151274

Hom.:

36156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.768

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.660

GnomAD3 exomes

AF:

0.653

AC:

100268

AN:

153474

Hom.:

33040

AF XY:

0.646

AC XY:

52348

AN XY:

81082

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.556

Gnomad EAS exome

AF:

0.814

Gnomad SAS exome

AF:

0.583

Gnomad FIN exome

AF:

0.714

Gnomad NFE exome

AF:

0.650

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.656

AC:

917568

AN:

1399050

Hom.:

302255

Cov.:

AF XY:

0.652

AC XY:

450212

AN XY:

690022

show subpopulations

Gnomad4 AFR exome

AF:

0.779

Gnomad4 AMR exome

AF:

0.615

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.815

Gnomad4 SAS exome

AF:

0.585

Gnomad4 FIN exome

AF:

0.716

Gnomad4 NFE exome

AF:

0.654

Gnomad4 OTH exome

AF:

0.658

GnomAD4 genome

AF:

0.687

AC:

104018

AN:

151390

Hom.:

36179

Cov.:

AF XY:

0.685

AC XY:

50677

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.767

Gnomad4 AMR

AF:

0.645

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.823

Gnomad4 SAS

AF:

0.596

Gnomad4 FIN

AF:

0.711

Gnomad4 NFE

AF:

0.650

Gnomad4 OTH

AF:

0.663

Alfa

AF:

0.627

Hom.:

8087

Bravo

AF:

0.688

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Alternating hemiplegia of childhood 2

Benign:2

Jul 14, 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

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. -

Dystonia 12

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 14, 2021

Genome-Nilou Lab

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

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 84% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 78. Only high quality variants are reported. -

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

Benign:1

Jul 14, 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

-0.58

CADD

Benign

8.4

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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