rs10517039

chr4-42511919-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006095.2(ATP8A1):c.1948-4765G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 152,054 control chromosomes in the GnomAD database, including 626 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 0.079 (626 hom., cov: 32)
• Consequence: ATP8A1 NM_006095.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

Genes affected

ATP8A1 (HGNC:13531): (ATPase phospholipid transporting 8A1) The P-type adenosinetriphosphatases (P-type ATPases) are a family of proteins which use the free energy of ATP hydrolysis to drive uphill transport of ions across membranes. Several subfamilies of P-type ATPases have been identified. One subfamily catalyzes transport of heavy metal ions. Another subfamily transports non-heavy metal ions (NMHI). The protein encoded by this gene is a member of the third subfamily of P-type ATPases and acts to transport amphipaths, such as phosphatidylserine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8A1	NM_006095.2	c.1948-4765G>T		intron_variant		ENST00000381668.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8A1	ENST00000381668.9	c.1948-4765G>T		intron_variant		1	NM_006095.2	A1
ATP8A1	ENST00000264449.14	c.1903-4765G>T		intron_variant		1		P3
ATP8A1	ENST00000700470.1	c.1903-4765G>T		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11911 AN: 151936 Hom.: 621 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0786 AC: 11948 AN: 152054 Hom.: 626 Cov.: 32 AF XY: 0.0771 AC XY: 5727 AN XY: 74328

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0762

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.0276

Gnomad4 SAS AF: 0.0625

Gnomad4 FIN AF: 0.0384

Gnomad4 NFE AF: 0.0467

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0685 Hom.: 76

Bravo AF: 0.0855

Asia WGS AF: 0.108 AC: 374 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.0
Dann	Benign	0.64

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

Other links and lift over

dbSNP: rs10517039; hg19: chr4-42513936;