15-25804250-T-C

Variant names:

• chr15-25804250-T-C
• rs4566129
• NM_024490.4:c.450-23027A>G

Variant summary

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

The NM_024490.4(ATP10A):​c.450-23027A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 150,628 control chromosomes in the GnomAD database, including 19,290 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 0.48 (19290 hom., cov: 29)
• Consequence: ATP10A NM_024490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 3 publications found

Genes affected

ATP10A (HGNC:13542): (ATPase phospholipid transporting 10A (putative)) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. This gene is maternally expressed. It maps within the most common interval of deletion responsible for Angelman syndrome, also known as 'happy puppet syndrome'. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024490.4. 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
	ATP10A	NM_024490.4	MANE Select	c.450-23027A>G		intron	N/A	NP_077816.1	O60312-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10A	ENST00000555815.7	TSL:5 MANE Select	c.450-23027A>G		intron	N/A	ENSP00000450480.2	O60312-1
	ATP10A	ENST00000356865.11	TSL:1	c.450-23027A>G		intron	N/A	ENSP00000349325.6	O60312-1
	ATP10A	ENST00000673747.1		c.450-23027A>G		intron	N/A	ENSP00000501230.1	A0A669KBE2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 71884 AN: 150506 Hom.: 19292 Cov.: 29

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.477 AC: 71909 AN: 150628 Hom.: 19290 Cov.: 29 AF XY: 0.485 AC XY: 35609 AN XY: 73474

African (AFR) AF: 0.219 AC: 8976 AN: 41024

American (AMR) AF: 0.578 AC: 8749 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1703 AN: 3458

East Asian (EAS) AF: 0.804 AC: 4026 AN: 5006

South Asian (SAS) AF: 0.557 AC: 2647 AN: 4756

European-Finnish (FIN) AF: 0.629 AC: 6482 AN: 10302

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.559 AC: 37845 AN: 67658

Other (OTH) AF: 0.452 AC: 944 AN: 2088

Alfa AF: 0.496 Hom.: 2363

Bravo AF: 0.467

Asia WGS AF: 0.655 AC: 2272 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.66
PhyloP100		0.56
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: rs4566129; hg19: chr15-26049397;