NM_001676.7:c.613A>C

Variant names:

• chr13-24690404-A-C
• rs142334583
• NM_001676.7:c.613A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001676.7(ATP12A):​c.613A>C​(p.Ile205Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I205F) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
• Consequence: ATP12A NM_001676.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12125194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP12A	NM_001676.7	c.613A>C	p.Ile205Leu	missense_variant	Exon 6 of 23	ENST00000381946.5	NP_001667.4
ATP12A	NM_001185085.2	c.613A>C	p.Ile205Leu	missense_variant	Exon 6 of 23		NP_001172014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP12A	ENST00000381946.5	c.613A>C	p.Ile205Leu	missense_variant	Exon 6 of 23	1	NM_001676.7	ENSP00000371372.3
ATP12A	ENST00000218548.10	c.613A>C	p.Ile205Leu	missense_variant	Exon 6 of 23	1		ENSP00000218548.6

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151008 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151008 Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1 AN XY: 73568

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.42
DEOGEN2	Benign	0.36	.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.63	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.25
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;B
Vest4		0.29
MutPred		0.56		Gain of catalytic residue at L200 (P = 0);Gain of catalytic residue at L200 (P = 0);
MVP		0.54
MPC		0.22
ClinPred		0.063	T
GERP RS		3.6
Varity_R		0.070
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs142334583; hg19: chr13-25264542;