13-24685326-C-T

Variant names:

• chr13-24685326-C-T
• NM_001676.7:c.181C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

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]

ACMG classification

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
ATP12A	NM_001676.7	c.181C>T	p.Leu61Phe	missense_variant	Exon 3 of 23	ENST00000381946.5	NP_001667.4
ATP12A	NM_001185085.2	c.181C>T	p.Leu61Phe	missense_variant	Exon 3 of 23		NP_001172014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP12A	ENST00000381946.5	c.181C>T	p.Leu61Phe	missense_variant	Exon 3 of 23	1	NM_001676.7	ENSP00000371372.3
ATP12A	ENST00000218548.10	c.181C>T	p.Leu61Phe	missense_variant	Exon 3 of 23	1		ENSP00000218548.6

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

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;