Genetic Variant ATP12A:p.Asn250Lys (chr13-24690672-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001676.7(ATP12A):c.750C>G(p.Asn250Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ATP12A
NM_001676.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.134

Publications

0 publications found

Variant links:

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]

ATP12A links:

ENSG00000285806 (HGNC:):

ENSG00000285806 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26749927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP12A	NM_001676.7 link	c.750C>G	p.Asn250Lys	missense_variant	Exon 7 of 23	ENST00000381946.5	NP_001667.4	P54707-1B4E0R9
ATP12A	NM_001185085.2 link	c.750C>G	p.Asn250Lys	missense_variant	Exon 7 of 23		NP_001172014.1	P54707-2B4E0R9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP12A	ENST00000381946.5 link	c.750C>G	p.Asn250Lys	missense_variant	Exon 7 of 23	1	NM_001676.7	ENSP00000371372.3	P54707-1
ATP12A	ENST00000218548.10 link	c.750C>G	p.Asn250Lys	missense_variant	Exon 7 of 23	1		ENSP00000218548.6	P54707-2
ENSG00000285806	ENST00000782956.1 link	n.281-1584G>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111974

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.750C>G (p.N250K) alteration is located in exon 7 (coding exon 7) of the ATP12A gene. This alteration results from a C to G substitution at nucleotide position 750, causing the asparagine (N) at amino acid position 250 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

0.0011

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

.;D

Eigen

Benign

-0.084

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.93

D;D

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.27

T;T

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

-0.13

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.79

P;P

Vest4

0.51

MutPred

0.53

Gain of methylation at N250 (P = 0.0024);Gain of methylation at N250 (P = 0.0024);

MVP

0.92

MPC

0.47

ClinPred

0.99

GERP RS

-1.7

Varity_R

0.44

gMVP

0.62

Mutation Taster

=63/37

polymorphism

(source)

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

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chr13-24690672-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over