chr13-112690441-C-G

Position:

• chr13-112690441-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015205.3(ATP11A):​c.25C>G​(p.Leu9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,206,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ATP11A NM_015205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

Genes affected

ATP11A (HGNC:13552): (ATPase phospholipid transporting 11A) The protein encoded by this gene is an integral membrane ATPase. The encoded protein is probably phosphorylated in its intermediate state and likely drives the transport of ions such as calcium across membranes. [provided by RefSeq, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13895997).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP11A	NM_015205.3	c.25C>G	p.Leu9Val	missense_variant	1/30	ENST00000375645.8	NP_056020.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP11A	ENST00000375645.8	c.25C>G	p.Leu9Val	missense_variant	1/30	5	NM_015205.3	ENSP00000364796	P1
ATP11A	ENST00000375630.6	c.25C>G	p.Leu9Val	missense_variant	1/29	5		ENSP00000364781
ATP11A	ENST00000487903.5	c.25C>G	p.Leu9Val	missense_variant	1/30	5		ENSP00000420387	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000497 AC: 6 AN: 1206298 Hom.: 0 Cov.: 30 AF XY: 0.00000339 AC XY: 2 AN XY: 589260

Gnomad4 AFR exome AF: 0.0000386

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000507

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.25C>G (p.L9V) alteration is located in exon 1 (coding exon 1) of the ATP11A gene. This alteration results from a C to G substitution at nucleotide position 25, causing the leucine (L) at amino acid position 9 to be replaced by a valine (V). 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	0.058
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	.;T;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N;.
MutationTaster	Benign	0.75	D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.060	N;N;N
REVEL	Benign	0.098
Sift	Benign	0.88	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.33
MutPred		0.35		Gain of catalytic residue at R12 (P = 0.0046);Gain of catalytic residue at R12 (P = 0.0046);Gain of catalytic residue at R12 (P = 0.0046);
MVP		0.30
MPC		0.30
ClinPred		0.23	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.47

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: rs1885011945; hg19: chr13-113344755;