NM_001676.7:c.571G>C

Variant names:

• chr13-24690362-G-C
• rs146053308
• NM_001676.7:c.571G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001676.7(ATP12A):​c.571G>C​(p.Glu191Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. E191K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ATP12A NM_001676.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52
• Publications: 1 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]

ENSG00000285806 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24015656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP12A	NM_001676.7	c.571G>C	p.Glu191Gln	missense_variant	Exon 6 of 23	ENST00000381946.5	NP_001667.4
ATP12A	NM_001185085.2	c.571G>C	p.Glu191Gln	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.571G>C	p.Glu191Gln	missense_variant	Exon 6 of 23	1	NM_001676.7	ENSP00000371372.3
ATP12A	ENST00000218548.10	c.571G>C	p.Glu191Gln	missense_variant	Exon 6 of 23	1		ENSP00000218548.6
ENSG00000285806	ENST00000782956.1	n.281-1274C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.072
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.64	N;N
PhyloP100		5.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.41
Sift	Benign	0.10	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.078	B;B
Vest4		0.31
MutPred		0.40		Loss of ubiquitination at K192 (P = 0.0486);Loss of ubiquitination at K192 (P = 0.0486);
MVP		0.93
MPC		0.28
ClinPred		0.74	D
GERP RS		3.9
Varity_R		0.26
gMVP		0.58
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs146053308; hg19: chr13-25264500;