15-25679748-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024490.4(ATP10A):c.4093G>A(p.Glu1365Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP10A NM_024490.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.427

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08017939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP10A	NM_024490.4	c.4093G>A	p.Glu1365Lys	missense_variant	21/21	ENST00000555815.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP10A	ENST00000555815.7	c.4093G>A	p.Glu1365Lys	missense_variant	21/21	5	NM_024490.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.4093G>A (p.E1365K) alteration is located in exon 21 (coding exon 21) of the ATP10A gene. This alteration results from a G to A substitution at nucleotide position 4093, causing the glutamic acid (E) at amino acid position 1365 to be replaced by a lysine (K). 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	0.084
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	13
Dann	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.75	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.018
Sift	Benign	0.20	T
Sift4G	Benign	0.44	T
Polyphen		0.28	B
Vest4		0.11
MutPred		0.20		Gain of ubiquitination at E1365 (P = 0.0029);
MVP		0.31
MPC		0.18
ClinPred		0.14	T
GERP RS		3.2
Varity_R		0.086
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-25924895;