rs4906796

Positions:

• chr15-25864661-C-G

Variant summary

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

The ENST00000389967.9(ATP10A):​c.-107+354G>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,240 control chromosomes in the GnomAD database, including 60,567 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 0.89 (60567 hom., cov: 33)
• Consequence: ATP10A ENST00000389967.9 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP10A	XM_005268261.5	c.-107+354G>C		intron_variant			XP_005268318.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP10A	ENST00000389967.9	c.-107+354G>C		intron_variant, NMD_transcript_variant		1		ENSP00000374617
ATP10A	ENST00000619904.1	c.-107+354G>C		intron_variant		5		ENSP00000480665

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135398 AN: 152120 Hom.: 60524 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.907

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

GnomAD4 genome AF: 0.890 AC: 135503 AN: 152240 Hom.: 60567 Cov.: 33 AF XY: 0.891 AC XY: 66351 AN XY: 74428

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.945

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.910

Alfa AF: 0.898 Hom.: 7644

Bravo AF: 0.886

Asia WGS AF: 0.884 AC: 3075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4906796; hg19: chr15-26109808;