19-41966810-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152296.5(ATP1A3):c.*127A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP1A3 NM_152296.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.112

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-41966810-T-G is Benign according to our data. Variant chr19-41966810-T-G is described in ClinVar as [Benign]. Clinvar id is 1263673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 1924 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1A3	NM_152296.5	c.*127A>C		3_prime_UTR_variant	23/23	ENST00000648268.1
ATP1A3	NM_001256213.2	c.*127A>C		3_prime_UTR_variant	23/23
ATP1A3	NM_001256214.2	c.*127A>C		3_prime_UTR_variant	23/23
ATP1A3	XM_047438862.1	c.*127A>C		3_prime_UTR_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1A3	ENST00000648268.1	c.*127A>C		3_prime_UTR_variant	23/23		NM_152296.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2945 AN: 36018 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.0892

Gnomad SAS AF: 0.0452

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0189 AC: 1924 AN: 101968 Hom.: 0 AF XY: 0.0170 AC XY: 930 AN XY: 54826

Gnomad AFR exome AF: 0.00239

Gnomad AMR exome AF: 0.000592

Gnomad ASJ exome AF: 0.00264

Gnomad EAS exome AF: 0.00350

Gnomad SAS exome AF: 0.000797

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00859

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00353 AC: 2591 AN: 733562 Hom.: 0 Cov.: 26 AF XY: 0.00345 AC XY: 1246 AN XY: 361216

Gnomad4 AFR exome AF: 0.000296

Gnomad4 AMR exome AF: 0.000325

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.000336

Gnomad4 SAS exome AF: 0.00332

Gnomad4 FIN exome AF: 0.0628

Gnomad4 NFE exome AF: 0.000841

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0818 AC: 2951 AN: 36068 Hom.: 0 Cov.: 0 AF XY: 0.0791 AC XY: 1364 AN XY: 17244

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.0637

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.0884

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0889

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0388 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	8.5
Dann	Benign	0.43

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

Other links and lift over

dbSNP: rs782239785; hg19: chr19-42470962; COSMIC: COSV57484779;