13-24685326-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001676.7(ATP12A):​c.181C>T​(p.Leu61Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

ATP12A
NM_001676.7 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41731548).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATP12ANM_001676.7 linkc.181C>T p.Leu61Phe missense_variant Exon 3 of 23 ENST00000381946.5 NP_001667.4 P54707-1B4E0R9
ATP12ANM_001185085.2 linkc.181C>T p.Leu61Phe missense_variant Exon 3 of 23 NP_001172014.1 P54707-2B4E0R9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP12AENST00000381946.5 linkc.181C>T p.Leu61Phe missense_variant Exon 3 of 23 1 NM_001676.7 ENSP00000371372.3 P54707-1
ATP12AENST00000218548.10 linkc.181C>T p.Leu61Phe missense_variant Exon 3 of 23 1 ENSP00000218548.6 P54707-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.181C>T (p.L61F) alteration is located in exon 3 (coding exon 3) of the ATP12A gene. This alteration results from a C to T substitution at nucleotide position 181, causing the leucine (L) at amino acid position 61 to be replaced by a phenylalanine (F). 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
Benign
0.14
BayesDel_addAF
Uncertain
0.036
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
.;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.087
D
MetaRNN
Benign
0.42
T;T
MetaSVM
Uncertain
0.39
D
MutationAssessor
Pathogenic
3.0
M;M
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-2.1
N;N
REVEL
Uncertain
0.51
Sift
Uncertain
0.0020
D;D
Sift4G
Benign
0.069
T;T
Polyphen
1.0
D;D
Vest4
0.26
MutPred
0.49
Gain of methylation at K60 (P = 0.0271);Gain of methylation at K60 (P = 0.0271);
MVP
0.94
MPC
0.82
ClinPred
0.97
D
GERP RS
4.4
Varity_R
0.38
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-25259464; API