rs771186944
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001676.7(ATP12A):c.724C>T(p.Arg242Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
ATP12A
NM_001676.7 missense
NM_001676.7 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 2.28
Publications
2 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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.851
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ATP12A | ENST00000381946.5 | c.724C>T | p.Arg242Cys | missense_variant | Exon 7 of 23 | 1 | NM_001676.7 | ENSP00000371372.3 | ||
| ATP12A | ENST00000218548.10 | c.724C>T | p.Arg242Cys | missense_variant | Exon 7 of 23 | 1 | ENSP00000218548.6 | |||
| ENSG00000285806 | ENST00000782956.1 | n.281-1558G>A | intron_variant | Intron 2 of 2 |
Frequencies
GnomAD3 genomes 0.0000329 AC: 5AN: 152072Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
5
AN:
152072
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000399 AC: 10AN: 250858 AF XY: 0.0000369 show subpopulations
GnomAD2 exomes
AF:
AC:
10
AN:
250858
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461672Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 727138 show subpopulations
GnomAD4 exome
AF:
AC:
36
AN:
1461672
Hom.:
Cov.:
33
AF XY:
AC XY:
19
AN XY:
727138
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33472
American (AMR)
AF:
AC:
4
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26106
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86220
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
30
AN:
1111926
Other (OTH)
AF:
AC:
1
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.476
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000329 AC: 5AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74276 show subpopulations
GnomAD4 genome
AF:
AC:
5
AN:
152072
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74276
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41402
American (AMR)
AF:
AC:
2
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5196
South Asian (SAS)
AF:
AC:
0
AN:
4806
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68010
Other (OTH)
AF:
AC:
1
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
5
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Mar 10, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.724C>T (p.R242C) alteration is located in exon 7 (coding exon 7) of the ATP12A gene. This alteration results from a C to T substitution at nucleotide position 724, causing the arginine (R) at amino acid position 242 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of catalytic residue at P241 (P = 0);Gain of catalytic residue at P241 (P = 0);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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