19-41966865-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152296.5(ATP1A3):c.*72A>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 0.0000686 in 1,546,304 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (1 hom., cov: 29)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: ATP1A3 NM_152296.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0370

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-41966865-T-C is Benign according to our data. Variant chr19-41966865-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1190789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00014 (21/150338) while in subpopulation AMR AF= 0.000795 (12/15090). AF 95% confidence interval is 0.000459. There are 1 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1A3	NM_152296.5	c.*72A>G		3_prime_UTR_variant	23/23	ENST00000648268.1
ATP1A3	NM_001256213.2	c.*72A>G		3_prime_UTR_variant	23/23
ATP1A3	NM_001256214.2	c.*72A>G		3_prime_UTR_variant	23/23
ATP1A3	XM_047438862.1	c.*72A>G		3_prime_UTR_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1A3	ENST00000648268.1	c.*72A>G		3_prime_UTR_variant	23/23		NM_152296.5

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 20 AN: 150224 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.0000737

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000796

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000218 AC: 33 AN: 151366 Hom.: 0 AF XY: 0.000212 AC XY: 17 AN XY: 80134

Gnomad AFR exome AF: 0.000122

Gnomad AMR exome AF: 0.000934

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000357

Gnomad SAS exome AF: 0.0000883

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000609 AC: 85 AN: 1395966 Hom.: 0 Cov.: 34 AF XY: 0.0000712 AC XY: 49 AN XY: 688550

Gnomad4 AFR exome AF: 0.000222

Gnomad4 AMR exome AF: 0.000673

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000560

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000130

Gnomad4 OTH exome AF: 0.000138

GnomAD4 genome AF: 0.000140 AC: 21 AN: 150338 Hom.: 1 Cov.: 29 AF XY: 0.000191 AC XY: 14 AN XY: 73326

Gnomad4 AFR AF: 0.0000980

Gnomad4 AMR AF: 0.000795

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000688 Hom.: 0

Bravo AF: 0.0000793

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	9.5
Dann	Uncertain	0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs186061886; hg19: chr19-42471017;