rs2289904

Positions:

• chr13-24701840-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001676.7(ATP12A):​c.1882-95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,517,908 control chromosomes in the GnomAD database, including 560 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (162 hom., cov: 33)
  • Exomes 𝑓: 0.019 (398 hom.)
• Consequence: ATP12A NM_001676.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

Genes affected

ATP12A (HGNC:13816): (ATPase H+/K+ transporting non-gastric alpha2 subunit) The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This gene encodes a catalytic subunit of the ouabain-sensitive H+/K+ -ATPase that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for potassium absorption in various tissues. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP12A	NM_001676.7	c.1882-95C>T		intron_variant		ENST00000381946.5
ATP12A	NM_001185085.2	c.1900-95C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP12A	ENST00000381946.5	c.1882-95C>T		intron_variant		1	NM_001676.7	A1
ATP12A	ENST00000218548.10	c.1900-95C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5279 AN: 152204 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0508

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.0187 AC: 25475 AN: 1365586 Hom.: 398 AF XY: 0.0190 AC XY: 12907 AN XY: 679190

Gnomad4 AFR exome AF: 0.0839

Gnomad4 AMR exome AF: 0.0118

Gnomad4 ASJ exome AF: 0.000579

Gnomad4 EAS exome AF: 0.0694

Gnomad4 SAS exome AF: 0.0279

Gnomad4 FIN exome AF: 0.00862

Gnomad4 NFE exome AF: 0.0151

Gnomad4 OTH exome AF: 0.0214

GnomAD4 genome AF: 0.0347 AC: 5285 AN: 152322 Hom.: 162 Cov.: 33 AF XY: 0.0336 AC XY: 2505 AN XY: 74500

Gnomad4 AFR AF: 0.0829

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.0505

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.00668

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0180 Hom.: 49

Bravo AF: 0.0382

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.60

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: rs2289904; hg19: chr13-25275978; COSMIC: COSV54520884; COSMIC: COSV54520884;