15-25680137-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_024490.4(ATP10A):c.3850G>A(p.Ala1284Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00811 in 1,613,716 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0084 (53 hom.)
• Consequence: ATP10A NM_024490.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.249

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009386629).
• BP6: Variant 15-25680137-C-T is Benign according to our data. Variant chr15-25680137-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP10A	NM_024490.4	c.3850G>A	p.Ala1284Thr	missense_variant	20/21	ENST00000555815.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP10A	ENST00000555815.7	c.3850G>A	p.Ala1284Thr	missense_variant	20/21	5	NM_024490.4	P1

Frequencies

GnomAD3 genomes AF: 0.00579 AC: 881 AN: 152144 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00293

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00903

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00580 AC: 1456 AN: 251132 Hom.: 4 AF XY: 0.00611 AC XY: 829 AN XY: 135686

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00447

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000850

Gnomad FIN exome AF: 0.00282

Gnomad NFE exome AF: 0.00995

Gnomad OTH exome AF: 0.00751

GnomAD4 exome AF: 0.00835 AC: 12208 AN: 1461454 Hom.: 53 Cov.: 33 AF XY: 0.00815 AC XY: 5926 AN XY: 727040

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.00444

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.00423

Gnomad4 NFE exome AF: 0.0100

Gnomad4 OTH exome AF: 0.00651

GnomAD4 genome AF: 0.00579 AC: 881 AN: 152262 Hom.: 2 Cov.: 33 AF XY: 0.00531 AC XY: 395 AN XY: 74424

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00293

Gnomad4 NFE AF: 0.00903

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00812 Hom.: 7

Bravo AF: 0.00618

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00882 AC: 34

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00895 AC: 77

ExAC AF: 0.00617 AC: 749

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0100

EpiControl AF: 0.0113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	ATP10A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	4.9
Dann	Benign	0.95
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.023
Sift	Benign	0.21	T
Sift4G	Benign	0.28	T
Polyphen		0.012	B
Vest4		0.36
MVP		0.21
MPC		0.16
ClinPred		0.0013	T
GERP RS		-2.6
Varity_R		0.047
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs116641809; hg19: chr15-25925284; COSMIC: COSV63514837; COSMIC: COSV63514837;