rs760297151

Variant names:

• chr20-51613735-C-T
• rs760297151
• NM_006045.3:c.2513G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006045.3(ATP9A):​c.2513G>A​(p.Arg838Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ATP9A NM_006045.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44

Genes affected

ATP9A (HGNC:13540): (ATPase phospholipid transporting 9A (putative)) Enables protease binding activity. Involved in negative regulation of exosomal secretion; regulation of endocytic recycling; and regulation of retrograde transport, endosome to Golgi. Located in several cellular components, including endosome membrane; perinuclear region of cytoplasm; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP9A	NM_006045.3	c.2513G>A	p.Arg838Gln	missense_variant	Exon 23 of 28	ENST00000338821.6	NP_006036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP9A	ENST00000338821.6	c.2513G>A	p.Arg838Gln	missense_variant	Exon 23 of 28	1	NM_006045.3	ENSP00000342481.5
ATP9A	ENST00000311637.9	c.2105G>A	p.Arg702Gln	missense_variant	Exon 18 of 23	1		ENSP00000309086.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251320 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461800 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2513G>A (p.R838Q) alteration is located in exon 23 (coding exon 23) of the ATP9A gene. This alteration results from a G to A substitution at nucleotide position 2513, causing the arginine (R) at amino acid position 838 to be replaced by a glutamine (Q). 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	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.56	D;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.44	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Pathogenic	3.9	.;H
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Pathogenic	0.89
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.048	D;D
Polyphen		1.0	.;D
Vest4		0.93
MutPred		0.78		.;Loss of MoRF binding (P = 0.0298);
MVP		0.94
MPC		1.7
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.54
gMVP		0.97

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: rs760297151; hg19: chr20-50230274;