13-24690456-C-T

Variant names:

• chr13-24690456-C-T
• rs200687022
• NM_001676.7:c.665C>T

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.665C>T​(p.Ser222Phe) 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. 15/22 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. S222Y) 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: 0.210
• Publications: 0 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=0.16577113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP12A	NM_001676.7	c.665C>T	p.Ser222Phe	missense_variant	Exon 6 of 23	ENST00000381946.5	NP_001667.4
ATP12A	NM_001185085.2	c.665C>T	p.Ser222Phe	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.665C>T	p.Ser222Phe	missense_variant	Exon 6 of 23	1	NM_001676.7	ENSP00000371372.3
ATP12A	ENST00000218548.10	c.665C>T	p.Ser222Phe	missense_variant	Exon 6 of 23	1		ENSP00000218548.6
ENSG00000285806	ENST00000782956.1	n.281-1368G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Pathogenic	0.83	.;D
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.2	M;M
PhyloP100		0.21
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.17
Sift	Benign	0.093	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0020	B;B
Vest4		0.28
MutPred		0.48		Loss of disorder (P = 0.0056);Loss of disorder (P = 0.0056);
MVP		0.82
MPC		0.24
ClinPred		0.11	T
GERP RS		1.1
Varity_R		0.15
gMVP		0.45
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs200687022; hg19: chr13-25264594;