rs3783139

Variant names:

• chr13-25966504-T-C
• rs3783139
• NM_016529.6:c.3273-2071T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-25966504-T-C
• chr13-25966504-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016529.6(ATP8A2):​c.3273-2071T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,240 control chromosomes in the GnomAD database, including 1,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1491 hom., cov: 32)
• Consequence: ATP8A2 NM_016529.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8A2	NM_016529.6	c.3273-2071T>C		intron_variant	Intron 34 of 36	ENST00000381655.7	NP_057613.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8A2	ENST00000381655.7	c.3273-2071T>C		intron_variant	Intron 34 of 36	1	NM_016529.6	ENSP00000371070.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15606 AN: 152122 Hom.: 1473 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.0942

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15644 AN: 152240 Hom.: 1491 Cov.: 32 AF XY: 0.108 AC XY: 8073 AN XY: 74438

African (AFR) AF: 0.0534 AC: 2221 AN: 41558

American (AMR) AF: 0.226 AC: 3457 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2581 AN: 5166

South Asian (SAS) AF: 0.113 AC: 545 AN: 4820

European-Finnish (FIN) AF: 0.0933 AC: 990 AN: 10610

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0794 AC: 5399 AN: 68012

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0952 Hom.: 1783

Bravo AF: 0.117

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.42
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism (auto)

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: rs3783139; hg19: chr13-26540642; COSMIC: COSV54974275;