NM_001676.7:c.547-107T>C

Variant names:

• chr13-24690231-T-C
• rs735770
• NM_001676.7:c.547-107T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001676.7(ATP12A):​c.547-107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,511,800 control chromosomes in the GnomAD database, including 47,807 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 0.23 (4638 hom., cov: 31)
  • Exomes 𝑓: 0.24 (43169 hom.)
• Consequence: ATP12A NM_001676.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 4 publications found

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]

ENSG00000285806 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001676.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP12A	NM_001676.7	MANE Select	c.547-107T>C		intron	N/A	NP_001667.4
	ATP12A	NM_001185085.2		c.547-107T>C		intron	N/A	NP_001172014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP12A	ENST00000381946.5	TSL:1 MANE Select	c.547-107T>C		intron	N/A	ENSP00000371372.3
	ATP12A	ENST00000218548.10	TSL:1	c.547-107T>C		intron	N/A	ENSP00000218548.6
	ENSG00000285806	ENST00000782956.1		n.281-1143A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35609 AN: 151704 Hom.: 4631 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.241 AC: 328330 AN: 1359978 Hom.: 43169 AF XY: 0.243 AC XY: 162842 AN XY: 671270

African (AFR) AF: 0.167 AC: 5135 AN: 30702

American (AMR) AF: 0.457 AC: 16465 AN: 35992

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 3844 AN: 21206

East Asian (EAS) AF: 0.505 AC: 19725 AN: 39036

South Asian (SAS) AF: 0.316 AC: 23317 AN: 73880

European-Finnish (FIN) AF: 0.207 AC: 9041 AN: 43682

Middle Eastern (MID) AF: 0.203 AC: 780 AN: 3838

European-Non Finnish (NFE) AF: 0.224 AC: 236355 AN: 1055380

Other (OTH) AF: 0.243 AC: 13668 AN: 56262

GnomAD4 genome AF: 0.235 AC: 35643 AN: 151822 Hom.: 4638 Cov.: 31 AF XY: 0.241 AC XY: 17887 AN XY: 74158

African (AFR) AF: 0.173 AC: 7148 AN: 41376

American (AMR) AF: 0.382 AC: 5831 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 643 AN: 3460

East Asian (EAS) AF: 0.475 AC: 2450 AN: 5158

South Asian (SAS) AF: 0.317 AC: 1521 AN: 4802

European-Finnish (FIN) AF: 0.219 AC: 2306 AN: 10552

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15087 AN: 67924

Other (OTH) AF: 0.212 AC: 446 AN: 2102

Alfa AF: 0.229 Hom.: 553

Bravo AF: 0.244

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs735770; hg19: chr13-25264369; COSMIC: COSV54516754;