Variant chr1-203698197-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001684.5(ATP2B4):c.234G>C(p.Gln78His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ATP2B4
NM_001684.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10

Variant links:

Genes affected

ATP2B4 (HGNC:817): (ATPase plasma membrane Ca2+ transporting 4) The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ATP2B4 links:

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ACMG classification

Classification made for transcript

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=0.079466075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATP2B4	NM_001684.5 linkuse as main transcript	c.234G>C	p.Gln78His	missense_variant	3/21	ENST00000357681.10
ATP2B4	NM_001001396.3 linkuse as main transcript	c.234G>C	p.Gln78His	missense_variant	3/22
ATP2B4	NM_001365783.2 linkuse as main transcript	c.234G>C	p.Gln78His	missense_variant	3/21
ATP2B4	NM_001365784.2 linkuse as main transcript	c.234G>C	p.Gln78His	missense_variant	3/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B4	ENST00000357681.10 linkuse as main transcript	c.234G>C	p.Gln78His	missense_variant	3/21	1	NM_001684.5	A1	P23634-6
ATP2B4	ENST00000341360.7 linkuse as main transcript	c.234G>C	p.Gln78His	missense_variant	3/22	1		P4	P23634-2
ATP2B4	ENST00000705901.1 linkuse as main transcript	c.234G>C	p.Gln78His	missense_variant	3/21				P23634-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.234G>C (p.Q78H) alteration is located in exon 3 (coding exon 2) of the ATP2B4 gene. This alteration results from a G to C substitution at nucleotide position 234, causing the glutamine (Q) at amino acid position 78 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.79

T;T;.

M_CAP

Benign

0.040

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.3

M;M;M

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.012

B;.;.

Vest4

0.21

MutPred

0.33

Loss of ubiquitination at K75 (P = 0.0755);Loss of ubiquitination at K75 (P = 0.0755);Loss of ubiquitination at K75 (P = 0.0755);

MVP

0.58

MPC

0.41

ClinPred

0.061

GERP RS

-2.1

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over