Variant chr13-25469044-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016529.6(ATP8A2):c.144A>C(p.Gly48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,613,836 control chromosomes in the GnomAD database, including 37,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4203 hom., cov: 33)

Exomes 𝑓: 0.21 ( 33361 hom. )

Consequence

ATP8A2
NM_016529.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

ATP8A2 (HGNC:13533): (ATPase phospholipid transporting 8A2) The protein encoded by this gene is a member of the P4 ATPase family of proteins, which are thought to be involved in a process called lipid flipping, whereby phospholipids are translocated inwards from the exoplasmic leaflet to the cytosolic leaflet of the cell membrane, which aids in generating and maintaining asymmetry in membrane lipids. This protein is predicted to contain an E1 E2 ATPase, a haloacid dehalogenase-like hydrolase (HAD) domain, and multiple transmembrane domains. Associations between this protein and cell cycle control protein 50A are important for translocation of phosphatidylserine across membranes. Mutations in this gene have been associated with a syndrome (CAMRQ4) characterized by cerebellar ataxia and cognitive disabilities. In addition, a translocation breakpoint within this gene was observed in an individual with neurological dysfunction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

ATP8A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 13-25469044-A-C is Benign according to our data. Variant chr13-25469044-A-C is described in ClinVar as [Benign]. Clinvar id is 128488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8A2	NM_016529.6 linkuse as main transcript	c.144A>C	p.Gly48=	synonymous_variant	2/37	ENST00000381655.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8A2	ENST00000381655.7 linkuse as main transcript	c.144A>C	p.Gly48=	synonymous_variant	2/37	1	NM_016529.6		Q9NTI2-4

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34414

AN:

152058

Hom.:

4188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.186

AC:

46331

AN:

249296

Hom.:

4749

AF XY:

0.185

AC XY:

25075

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.0907

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.210

AC:

307205

AN:

1461662

Hom.:

33361

Cov.:

AF XY:

0.208

AC XY:

151457

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.199

GnomAD4 genome

AF:

0.227

AC:

34473

AN:

152174

Hom.:

4203

Cov.:

AF XY:

0.221

AC XY:

16463

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.221

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.214

Hom.:

5679

Bravo

AF:

0.224

Asia WGS

AF:

0.151

AC:

524

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.211

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over