chr15-25681032-C-T

Position:

• chr15-25681032-C-T

Variant summary

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

The NM_024490.4(ATP10A):​c.3535G>A​(p.Ala1179Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,612,706 control chromosomes in the GnomAD database, including 30,255 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.25 (5879 hom., cov: 32)
  • Exomes 𝑓: 0.17 (24376 hom.)
• Consequence: ATP10A NM_024490.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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]

ATP10A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.0230155E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP10A	NM_024490.4	c.3535G>A	p.Ala1179Thr	missense_variant	18/21	ENST00000555815.7	NP_077816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP10A	ENST00000555815.7	c.3535G>A	p.Ala1179Thr	missense_variant	18/21	5	NM_024490.4	ENSP00000450480.2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38238 AN: 151950 Hom.: 5859 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.254

GnomAD3 exomes AF: 0.208 AC: 52352 AN: 251178 Hom.: 6764 AF XY: 0.194 AC XY: 26356 AN XY: 135748

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.361

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.171 AC: 249790 AN: 1460638 Hom.: 24376 Cov.: 43 AF XY: 0.169 AC XY: 122534 AN XY: 726618

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.252 AC: 38319 AN: 152068 Hom.: 5879 Cov.: 32 AF XY: 0.253 AC XY: 18778 AN XY: 74322

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.251

Alfa AF: 0.190 Hom.: 4709

Bravo AF: 0.277

TwinsUK AF: 0.151 AC: 560

ALSPAC AF: 0.147 AC: 568

ESP6500AA AF: 0.417 AC: 1839

ESP6500EA AF: 0.160 AC: 1378

ExAC AF: 0.202 AC: 24522

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.0
DANN	Benign	0.95
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.00040	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.036
Sift	Benign	0.067	T
Sift4G	Uncertain	0.056	T
Polyphen		0.64	P
Vest4		0.068
MPC		0.16
ClinPred		0.012	T
GERP RS		0.30
Varity_R		0.073
gMVP		0.46

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: rs2076744; hg19: chr15-25926179; COSMIC: COSV63514539; COSMIC: COSV63514539;