13-113649442-C-A

Variant names:

• chr13-113649442-C-A
• rs764891890
• NM_000705.4:c.808G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000705.4(ATP4B):​c.808G>T​(p.Val270Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,426,308 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V270M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ATP4B NM_000705.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65
• Publications: 0 publications found

Genes affected

ATP4B (HGNC:820): (ATPase H+/K+ transporting subunit beta) The protein encoded by this gene belongs to a family of P-type cation-transporting ATPases. The gastric H+, K+-ATPase is a heterodimer consisting of a high molecular weight catalytic alpha subunit and a smaller but heavily glycosylated beta subunit. This enzyme is a proton pump that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for gastric acid secretion. This gene encodes the beta subunit of the gastric H+, K+-ATPase. [provided by RefSeq, Jul 2008]

GRK1 (HGNC:10013): (G protein-coupled receptor kinase 1) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates rhodopsin and initiates its deactivation. Defects in GRK1 are known to cause Oguchi disease 2 (also known as stationary night blindness Oguchi type-2). [provided by RefSeq, Jul 2008]

GRK1 Gene-Disease associations (from GenCC):

• Oguchi disease

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Oguchi disease-2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2770012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000705.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP4B	NM_000705.4	MANE Select	c.808G>T	p.Val270Leu	missense	Exon 7 of 7	NP_000696.1	P51164

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP4B	ENST00000335288.5	TSL:1 MANE Select	c.808G>T	p.Val270Leu	missense	Exon 7 of 7	ENSP00000334216.3	P51164

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426308 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 706214

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32778

American (AMR) AF: 0.0000245 AC: 1 AN: 40782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25548

East Asian (EAS) AF: 0.00 AC: 0 AN: 38122

South Asian (SAS) AF: 0.00 AC: 0 AN: 81896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5162

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092088

Other (OTH) AF: 0.00 AC: 0 AN: 58934

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	0.083
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.73	N
PhyloP100		4.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.16
Sift	Benign	0.41	T
Sift4G	Benign	0.37	T
Polyphen		0.89	P
Vest4		0.38
MutPred		0.62		Loss of catalytic residue at V270 (P = 0.0552)
MVP		0.30
MPC		0.27
ClinPred		0.73	D
GERP RS		3.6
Varity_R		0.067
gMVP		0.63
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs764891890; hg19: chr13-114303757;