15-25697158-C-G

Variant names:

• chr15-25697158-C-G
• rs4906747
• NM_024490.4:c.2761-2012G>C

Variant summary

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

The NM_024490.4(ATP10A):​c.2761-2012G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,218 control chromosomes in the GnomAD database, including 911 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 (911 hom., cov: 33)
• Consequence: ATP10A NM_024490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 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.2761-2012G>C		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.2761-2012G>C		intron	N/A	ENSP00000450480.2	O60312-1
	ATP10A	ENST00000356865.11	TSL:1	c.2761-2012G>C		intron	N/A	ENSP00000349325.6	O60312-1
	ATP10A	ENST00000673680.1		n.3423-2012G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15578 AN: 152100 Hom.: 912 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.0836

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.0853

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

GnomAD4 genome AF: 0.102 AC: 15581 AN: 152218 Hom.: 911 Cov.: 33 AF XY: 0.107 AC XY: 7978 AN XY: 74422

African (AFR) AF: 0.110 AC: 4555 AN: 41524

American (AMR) AF: 0.0709 AC: 1084 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3470

East Asian (EAS) AF: 0.0832 AC: 431 AN: 5178

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4824

European-Finnish (FIN) AF: 0.142 AC: 1508 AN: 10600

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0943 AC: 6411 AN: 68012

Other (OTH) AF: 0.0835 AC: 176 AN: 2108

Alfa AF: 0.0459 Hom.: 30

Bravo AF: 0.0934

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.4
DANN	Benign	0.83
PhyloP100		-0.13
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: rs4906747; hg19: chr15-25942305;