chr13-24688392-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001676.7(ATP12A):​c.302C>T​(p.Thr101Met) variant causes a missense change. The variant allele was found at a frequency of 0.000194 in 1,614,064 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 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

ATP12A
NM_001676.7 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATP12ANM_001676.7 linkuse as main transcriptc.302C>T p.Thr101Met missense_variant 4/23 ENST00000381946.5 NP_001667.4 P54707-1B4E0R9
ATP12ANM_001185085.2 linkuse as main transcriptc.302C>T p.Thr101Met missense_variant 4/23 NP_001172014.1 P54707-2B4E0R9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATP12AENST00000381946.5 linkuse as main transcriptc.302C>T p.Thr101Met missense_variant 4/231 NM_001676.7 ENSP00000371372.3 P54707-1
ATP12AENST00000218548.10 linkuse as main transcriptc.302C>T p.Thr101Met missense_variant 4/231 ENSP00000218548.6 P54707-2

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000279
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000116
AC:
29
AN:
250476
Hom.:
0
AF XY:
0.000148
AC XY:
20
AN XY:
135454
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000213
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000198
AC:
289
AN:
1461868
Hom.:
0
Cov.:
31
AF XY:
0.000209
AC XY:
152
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000241
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000246
Hom.:
0
Bravo
AF:
0.000110
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000123
AC:
15
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 26, 2024The c.302C>T (p.T101M) alteration is located in exon 4 (coding exon 4) of the ATP12A gene. This alteration results from a C to T substitution at nucleotide position 302, causing the threonine (T) at amino acid position 101 to be replaced by a methionine (M). 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
0.092
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Uncertain
-0.010
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.76
.;D
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
0.64
D
MutationAssessor
Pathogenic
3.3
M;M
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-4.3
D;D
REVEL
Uncertain
0.56
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
D;D
Vest4
0.76
MVP
0.96
MPC
0.80
ClinPred
0.85
D
GERP RS
5.1
Varity_R
0.39
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146927457; hg19: chr13-25262530; COSMIC: COSV54513391; API