Variant 15-25679762-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024490.4(ATP10A):c.4079C>T(p.Pro1360Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,613,122 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 5 hom. )

Consequence

ATP10A
NM_024490.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009170085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP10A	NM_024490.4 linkuse as main transcript	c.4079C>T	p.Pro1360Leu	missense_variant	21/21	ENST00000555815.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP10A	ENST00000555815.7 linkuse as main transcript	c.4079C>T	p.Pro1360Leu	missense_variant	21/21	5	NM_024490.4	P1	O60312-1

Frequencies

GnomAD3 genomes

AF:

0.000867

AC:

132

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000760

AC:

190

AN:

250022

Hom.:

AF XY:

0.000798

AC XY:

108

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.000500

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.00120

AC:

1748

AN:

1460834

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

887

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.000133

Gnomad4 NFE exome

AF:

0.00144

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.000867

AC:

132

AN:

152288

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.000914

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.000782

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00136

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2021

The c.4079C>T (p.P1360L) alteration is located in exon 21 (coding exon 21) of the ATP10A gene. This alteration results from a C to T substitution at nucleotide position 4079, causing the proline (P) at amino acid position 1360 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

Cadd

Benign

9.6

Dann

Benign

0.67

DEOGEN2

Benign

0.032

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.65

M_CAP

Benign

0.012

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.42

MutationTaster

Benign

0.54

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

REVEL

Benign

0.041

Sift

Benign

0.28

Sift4G

Benign

0.10

Polyphen

0.0030

Vest4

0.056

MVP

0.068

MPC

0.16

ClinPred

0.017

GERP RS

2.5

Varity_R

0.019

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over