rs2137696587

Variant names:

• chr13-24690605-T-A
• rs2137696587
• NM_001676.7:c.683T>A

Your query was ambiguous. Multiple possible variants found:

• chr13-24690605-T-A
• chr13-24690605-T-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001676.7(ATP12A):​c.683T>A​(p.Val228Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. V228A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP12A NM_001676.7 missense, splice_region
• Scores: Splicing: ADA: 0.5587
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.80
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP12A	NM_001676.7	c.683T>A	p.Val228Glu	missense_variant, splice_region_variant	Exon 7 of 23	ENST00000381946.5	NP_001667.4
ATP12A	NM_001185085.2	c.683T>A	p.Val228Glu	missense_variant, splice_region_variant	Exon 7 of 23		NP_001172014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP12A	ENST00000381946.5	c.683T>A	p.Val228Glu	missense_variant, splice_region_variant	Exon 7 of 23	1	NM_001676.7	ENSP00000371372.3
ATP12A	ENST00000218548.10	c.683T>A	p.Val228Glu	missense_variant, splice_region_variant	Exon 7 of 23	1		ENSP00000218548.6
ENSG00000285806	ENST00000782956.1	n.281-1517A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.96	.;D
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.7	H;H
PhyloP100		7.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.98
MutPred		0.76		Gain of catalytic residue at L233 (P = 0.0254);Gain of catalytic residue at L233 (P = 0.0254);
MVP		1.0
MPC		1.1
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.95
gMVP		0.90
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.56
dbscSNV1_RF	Benign	0.36
SpliceAI score (max)		0.18		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: rs2137696587; hg19: chr13-25264743;